Genetic Variant SLC9A3:c.211+3131G>A (chr5-520981-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004174.4(SLC9A3):c.211+3131G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 152,084 control chromosomes in the GnomAD database, including 17,876 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.48 ( 17876 hom., cov: 33)

Consequence

SLC9A3
NM_004174.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.98

Publications

7 publications found

Variant links:

Genes affected

SLC9A3 (HGNC:11073): (solute carrier family 9 member A3) The protein encoded by this gene is an epithelial brush border Na/H exchanger that uses an inward sodium ion gradient to expel acids from the cell. Defects in this gene are a cause of congenital secretory sodium diarrhea. Pseudogenes of this gene exist on chromosomes 10 and 22. [provided by RefSeq, Mar 2016]

SLC9A3 Gene-Disease associations (from GenCC):

congenital secretory sodium diarrhea 8
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
congenital sodium diarrhea
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
cystic fibrosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SLC9A3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A3	NM_004174.4 link	c.211+3131G>A		intron_variant	Intron 1 of 16	ENST00000264938.8	NP_004165.2
SLC9A3	NM_001284351.3 link	c.211+3131G>A		intron_variant	Intron 1 of 16		NP_001271280.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
SLC9A3	ENST00000264938.8 link	c.211+3131G>A	intron_variant	Intron 1 of 16	1	NM_004174.4	ENSP00000264938.3
SLC9A3	ENST00000514375.1 link	c.211+3131G>A	intron_variant	Intron 1 of 16	1		ENSP00000422983.1
SLC9A3	ENST00000644203.1 link	c.211+3131G>A	intron_variant	Intron 1 of 15			ENSP00000495903.1

Frequencies

GnomAD3 genomes

AF:

0.476

AC:

72403

AN:

151966

Hom.:

17844

Cov.:

show subpopulations

Gnomad AFR

AF:

0.560

Gnomad AMI

AF:

0.512

Gnomad AMR

AF:

0.464

Gnomad ASJ

AF:

0.512

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.349

Gnomad FIN

AF:

0.410

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.471

Gnomad OTH

AF:

0.460

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.477

AC:

72484

AN:

152084

Hom.:

17876

Cov.:

AF XY:

0.471

AC XY:

35003

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.561

AC:

23266

AN:

41496

American (AMR)

AF:

0.463

AC:

7077

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.512

AC:

1776

AN:

3470

East Asian (EAS)

AF:

0.154

AC:

798

AN:

5180

South Asian (SAS)

AF:

0.351

AC:

1695

AN:

4824

European-Finnish (FIN)

AF:

0.410

AC:

4340

AN:

10588

Middle Eastern (MID)

AF:

0.476

AC:

140

AN:

294

European-Non Finnish (NFE)

AF:

0.471

AC:

31962

AN:

67918

Other (OTH)

AF:

0.456

AC:

963

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1960

3920

5881

7841

9801

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

648

1296

1944

2592

3240

<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:

0.481

Hom.:

3488

Bravo

AF:

0.484

Asia WGS

AF:

0.277

AC:

963

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.14

(source)

DANN

Benign

0.56

PhyloP100

-3.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over