rs869320759

Variant names:

• chr5-484669-GC-G
• NM_004174.4:c.782delG

Your query was ambiguous. Multiple possible variants found:

• chr5-484669-GC-G
• chr5-484669-GC-GCC

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_004174.4(SLC9A3):​c.782delG​(p.Gly261AlafsTer15) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000205 in 1,460,666 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC9A3 NM_004174.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.91

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]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A3	NM_004174.4	c.782delG	p.Gly261AlafsTer15	frameshift_variant	Exon 5 of 17	ENST00000264938.8	NP_004165.2
SLC9A3	NM_001284351.3	c.782delG	p.Gly261AlafsTer15	frameshift_variant	Exon 5 of 17		NP_001271280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A3	ENST00000264938.8	c.782delG	p.Gly261AlafsTer15	frameshift_variant	Exon 5 of 17	1	NM_004174.4	ENSP00000264938.3
SLC9A3	ENST00000514375.1	c.782delG	p.Gly261AlafsTer15	frameshift_variant	Exon 5 of 17	1		ENSP00000422983.1
SLC9A3	ENST00000644203.1	c.782delG	p.Gly261AlafsTer15	frameshift_variant	Exon 5 of 16			ENSP00000495903.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460666 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726656

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-484784;