15-74181398-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBA1

The NM_022369.4(STRA6):c.1581G>A(p.Met527Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,613,538 control chromosomes in the GnomAD database, including 15,095 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1292 hom., cov: 31)

Exomes 𝑓: 0.12 ( 13803 hom. )

Consequence

STRA6
NM_022369.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.382

Publications

44 publications found

Variant links:

Genes affected

STRA6 (HGNC:30650): (signaling receptor and transporter of retinol STRA6) The protein encoded by this gene is a membrane protein involved in the metabolism of retinol. The encoded protein acts as a receptor for retinol/retinol binding protein complexes. This protein removes the retinol from the complex and transports it across the cell membrane. Defects in this gene are a cause of syndromic microphthalmia type 9 (MCOPS9). Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

STRA6 Gene-Disease associations (from GenCC):

Matthew-Wood syndrome
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Orphanet
microphthalmia, isolated, with coloboma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

STRA6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 15-74181398-C-T is Benign according to our data. Variant chr15-74181398-C-T is described in ClinVar as Benign. ClinVar VariationId is 261578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022369.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
STRA6	NM_022369.4	MANE Select	c.1581G>A	p.Met527Ile	missense	Exon 17 of 19	NP_071764.3
STRA6	NM_001199042.2		c.1698G>A	p.Met566Ile	missense	Exon 17 of 19	NP_001185971.1
STRA6	NM_001199040.2		c.1692G>A	p.Met564Ile	missense	Exon 17 of 19	NP_001185969.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
STRA6	ENST00000395105.9	TSL:1 MANE Select	c.1581G>A	p.Met527Ile	missense	Exon 17 of 19	ENSP00000378537.4
STRA6	ENST00000563965.5	TSL:1	c.1698G>A	p.Met566Ile	missense	Exon 17 of 19	ENSP00000456609.1
STRA6	ENST00000423167.6	TSL:1	c.1554G>A	p.Met518Ile	missense	Exon 17 of 19	ENSP00000413012.2

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17237

AN:

151742

Hom.:

1295

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0865

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.340

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0870

Gnomad OTH

AF:

0.0971

GnomAD2 exomes

AF:

0.162

AC:

40521

AN:

250820

AF XY:

0.162

show subpopulations

Gnomad AFR exome

AF:

0.0840

Gnomad AMR exome

AF:

0.276

Gnomad ASJ exome

AF:

0.124

Gnomad EAS exome

AF:

0.333

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.0875

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.116

AC:

170199

AN:

1461678

Hom.:

13803

Cov.:

AF XY:

0.121

AC XY:

87983

AN XY:

727132

show subpopulations

African (AFR)

AF:

0.0788

AC:

2638

AN:

33478

American (AMR)

AF:

0.262

AC:

11703

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

3327

AN:

26134

East Asian (EAS)

AF:

0.340

AC:

13488

AN:

39696

South Asian (SAS)

AF:

0.295

AC:

25462

AN:

86218

European-Finnish (FIN)

AF:

0.111

AC:

5937

AN:

53338

Middle Eastern (MID)

AF:

0.0954

AC:

550

AN:

5768

European-Non Finnish (NFE)

AF:

0.0893

AC:

99309

AN:

1111978

Other (OTH)

AF:

0.129

AC:

7785

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

9115

18230

27345

36460

45575

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4066

8132

12198

16264

20330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.113

AC:

17229

AN:

151860

Hom.:

1292

Cov.:

AF XY:

0.120

AC XY:

8902

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.0862

AC:

3574

AN:

41444

American (AMR)

AF:

0.162

AC:

2471

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.123

AC:

425

AN:

3466

East Asian (EAS)

AF:

0.340

AC:

1734

AN:

5102

South Asian (SAS)

AF:

0.297

AC:

1421

AN:

4784

European-Finnish (FIN)

AF:

0.130

AC:

1374

AN:

10578

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0870

AC:

5907

AN:

67916

Other (OTH)

AF:

0.0951

AC:

200

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

718

1436

2155

2873

3591

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

214

428

642

856

1070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.100

Hom.:

3697

Bravo

AF:

0.114

TwinsUK

AF:

0.0860

AC:

319

ALSPAC

AF:

0.0838

AC:

323

ESP6500AA

AF:

0.0889

AC:

391

ESP6500EA

AF:

0.0860

AC:

739

ExAC

AF:

0.157

AC:

19101

Asia WGS

AF:

0.327

AC:

1135

AN:

3478

EpiCase

AF:

0.0899

EpiControl

AF:

0.0859

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Matthew-Wood syndrome (2)

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.090

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0055

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

0.38

PrimateAI

Benign

0.29

PROVEAN

Benign

0.20

REVEL

Benign

0.15

Sift

Benign

0.85

Sift4G

Benign

0.23

Polyphen

0.0

Vest4

0.049

MutPred

0.14

Gain of catalytic residue at M527 (P = 0.109)

MPC

0.10

ClinPred

0.011

GERP RS

3.8

Varity_R

0.044

gMVP

0.20

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.62

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.62

Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over