NM_004174.4:c.211+3131G>A

Variant names:

• chr5-520981-C-T
• rs4957061
• NM_004174.4:c.211+3131G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98
• Publications: 7 publications found

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004174.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A3	NM_004174.4	MANE Select	c.211+3131G>A		intron	N/A	NP_004165.2
	SLC9A3	NM_001284351.3		c.211+3131G>A		intron	N/A	NP_001271280.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A3	ENST00000264938.8	TSL:1 MANE Select	c.211+3131G>A		intron	N/A	ENSP00000264938.3
	SLC9A3	ENST00000514375.1	TSL:1	c.211+3131G>A		intron	N/A	ENSP00000422983.1
	SLC9A3	ENST00000644203.1		c.211+3131G>A		intron	N/A	ENSP00000495903.1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72403 AN: 151966 Hom.: 17844 Cov.: 33

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.: 33 AF XY: 0.471 AC XY: 35003 AN XY: 74370

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.14
DANN	Benign	0.56
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4957061; hg19: chr5-521096; COSMIC: COSV53804851; COSMIC: COSV53804851;