Genetic Variant STRA6:p.Leu152Met (chr15-74195628-A-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000432245.6(STRA6):c.454T>A(p.Leu152Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,543,242 control chromosomes in the GnomAD database, including 30,271 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2026 hom., cov: 32)

Exomes 𝑓: 0.19 ( 28245 hom. )

Consequence

STRA6
ENST00000432245.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.425

Publications

20 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003751129).

BP6

Variant 15-74195628-A-T is Benign according to our data. Variant chr15-74195628-A-T is described in ClinVar as Benign. ClinVar VariationId is 1183162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRA6	NM_022369.4 link	c.430+24T>A		intron_variant	Intron 6 of 18	ENST00000395105.9	NP_071764.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRA6	ENST00000395105.9 link	c.430+24T>A		intron_variant	Intron 6 of 18	1	NM_022369.4	ENSP00000378537.4

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21038

AN:

151704

Hom.:

2026

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0369

Gnomad AMI

AF:

0.135

Gnomad AMR

AF:

0.0862

Gnomad ASJ

AF:

0.188

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0327

Gnomad FIN

AF:

0.259

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.113

GnomAD2 exomes

AF:

0.138

AC:

21697

AN:

156878

AF XY:

0.136

show subpopulations

Gnomad AFR exome

AF:

0.0323

Gnomad AMR exome

AF:

0.0684

Gnomad ASJ exome

AF:

0.180

Gnomad EAS exome

AF:

0.000351

Gnomad FIN exome

AF:

0.257

Gnomad NFE exome

AF:

0.206

Gnomad OTH exome

AF:

0.142

GnomAD4 exome

AF:

0.190

AC:

263920

AN:

1391420

Hom.:

28245

Cov.:

AF XY:

0.185

AC XY:

127364

AN XY:

686706

show subpopulations

African (AFR)

AF:

0.0276

AC:

869

AN:

31484

American (AMR)

AF:

0.0692

AC:

2469

AN:

35696

Ashkenazi Jewish (ASJ)

AF:

0.185

AC:

4649

AN:

25132

East Asian (EAS)

AF:

0.000280

AC:

AN:

35774

South Asian (SAS)

AF:

0.0476

AC:

3766

AN:

79112

European-Finnish (FIN)

AF:

0.264

AC:

13022

AN:

49292

Middle Eastern (MID)

AF:

0.0494

AC:

281

AN:

5694

European-Non Finnish (NFE)

AF:

0.214

AC:

229260

AN:

1071502

Other (OTH)

AF:

0.166

AC:

9594

AN:

57734

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

10239

20477

30716

40954

51193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7852

15704

23556

31408

39260

<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:

0.139

AC:

21034

AN:

151822

Hom.:

2026

Cov.:

AF XY:

0.137

AC XY:

10125

AN XY:

74172

show subpopulations

African (AFR)

AF:

0.0368

AC:

1522

AN:

41404

American (AMR)

AF:

0.0860

AC:

1312

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.188

AC:

651

AN:

3468

East Asian (EAS)

AF:

0.00136

AC:

AN:

5158

South Asian (SAS)

AF:

0.0321

AC:

154

AN:

4800

European-Finnish (FIN)

AF:

0.259

AC:

2728

AN:

10534

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.210

AC:

14283

AN:

67894

Other (OTH)

AF:

0.112

AC:

236

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

899

1797

2696

3594

4493

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

226

452

678

904

1130

<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:

0.193

Hom.:

2356

Bravo

AF:

0.121

TwinsUK

AF:

0.222

AC:

823

ALSPAC

AF:

0.213

AC:

820

ESP6500AA

AF:

0.0374

AC:

ESP6500EA

AF:

0.218

AC:

1006

ExAC

AF:

0.0814

AC:

5474

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

7.5

(source)

DANN

Benign

0.94

Eigen

Benign

-0.81

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.19

MetaRNN

Benign

0.0038

MetaSVM

Benign

-1.1

PhyloP100

0.42

PROVEAN

Benign

-0.64

REVEL

Benign

0.23

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.90

Vest4

0.14

ClinPred

0.0074

GERP RS

-2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over