Genetic Variant SLC45A4:p.Asn613Ser (chr8-141215862-T-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001286646.2(SLC45A4):c.1838A>G(p.Asn613Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00894 in 1,614,124 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0091 ( 75 hom. )

Consequence

SLC45A4
NM_001286646.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.04

Publications

12 publications found

Variant links:

Genes affected

SLC45A4 (HGNC:29196): (solute carrier family 45 member 4) Predicted to enable sucrose:proton symporter activity. Predicted to be involved in sucrose transport. Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC45A4 links:

ENSG00000296050 (HGNC:):

ENSG00000296050 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009536624).

BP6

Variant 8-141215862-T-C is Benign according to our data. Variant chr8-141215862-T-C is described in ClinVar as Benign. ClinVar VariationId is 773507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC45A4	NM_001286646.2 link	c.1838A>G	p.Asn613Ser	missense_variant	Exon 7 of 9	ENST00000517878.6	NP_001273575.1	Q5BKX6E7EV90B2RXG1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC45A4	ENST00000517878.6 link	c.1838A>G	p.Asn613Ser	missense_variant	Exon 7 of 9	1	NM_001286646.2	ENSP00000428137.1	E7EV90
SLC45A4	ENST00000024061.7 link	c.1685A>G	p.Asn562Ser	missense_variant	Exon 6 of 8	1		ENSP00000024061.3	Q5BKX6-3
SLC45A4	ENST00000519067.5 link	c.1685A>G	p.Asn562Ser	missense_variant	Exon 6 of 7	1		ENSP00000429059.1	Q5BKX6-2
ENSG00000296050	ENST00000735948.1 link	n.133-6737T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.00756

AC:

1150

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.00569

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0205

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0106

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00702

AC:

1764

AN:

251380

AF XY:

0.00705

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00278

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0227

Gnomad NFE exome

AF:

0.00939

Gnomad OTH exome

AF:

0.00587

GnomAD4 exome

AF:

0.00908

AC:

13277

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00905

AC XY:

6579

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00134

AC:

AN:

33480

American (AMR)

AF:

0.00313

AC:

140

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00150

AC:

129

AN:

86258

European-Finnish (FIN)

AF:

0.0218

AC:

1163

AN:

53386

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0102

AC:

11304

AN:

1112006

Other (OTH)

AF:

0.00796

AC:

481

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

697

1394

2091

2788

3485

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.00755

AC:

1150

AN:

152270

Hom.:

Cov.:

AF XY:

0.00790

AC XY:

588

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00169

AC:

AN:

41542

American (AMR)

AF:

0.00569

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0205

AC:

218

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0106

AC:

721

AN:

68004

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

119

178

238

297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00892

Hom.:

Bravo

AF:

0.00623

TwinsUK

AF:

0.00998

AC:

ALSPAC

AF:

0.0112

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00988

AC:

ExAC

AF:

0.00635

AC:

771

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00769

EpiControl

AF:

0.00836

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 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

.;T;.

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.11

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

D;D;D

MetaRNN

Benign

0.0095

T;T;T

MetaSVM

Uncertain

0.19

PhyloP100

6.0

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-4.0

D;D;D

REVEL

Uncertain

0.40

Sift

Benign

0.12

T;T;T

Sift4G

Benign

0.11

T;T;T

Polyphen

0.34

B;B;P

Vest4

0.56

MVP

0.83

MPC

0.31

ClinPred

0.057

GERP RS

4.2

gMVP

0.70

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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