rs776437567

Variant names:

• chr20-49815094-C-G
• rs776437567
• NM_015266.3:c.113C>G

Your query was ambiguous. Multiple possible variants found:

• chr20-49815094-C-G
• chr20-49815094-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015266.3(SLC9A8):​c.113C>G​(p.Pro38Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,456,832 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC9A8 NM_015266.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.73

Genes affected

SLC9A8 (HGNC:20728): (solute carrier family 9 member A8) Sodium-hydrogen exchangers (NHEs), such as SLC9A8, are integral transmembrane proteins that exchange extracellular Na+ for intracellular H+. NHEs have multiple functions, including intracellular pH homeostasis, cell volume regulation, and electroneutral NaCl absorption in epithelia (Xu et al., 2008 [PubMed 18209477]).[supplied by OMIM, Apr 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30248302).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A8	NM_015266.3	c.113C>G	p.Pro38Arg	missense_variant	Exon 2 of 16	ENST00000361573.3	NP_056081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A8	ENST00000361573.3	c.113C>G	p.Pro38Arg	missense_variant	Exon 2 of 16	1	NM_015266.3	ENSP00000354966.2
SLC9A8	ENST00000417961.5	c.113C>G	p.Pro38Arg	missense_variant	Exon 2 of 16	2		ENSP00000416418.1
SLC9A8	ENST00000489787.1	n.142C>G		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456832 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724532

Gnomad4 AFR exome AF: 0.0000301

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.087
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.93	P;P
Vest4		0.44
MutPred		0.39		Loss of glycosylation at P38 (P = 0.0215);Loss of glycosylation at P38 (P = 0.0215);
MVP		0.90
MPC		1.0
ClinPred		0.72	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.63

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

LitVar

Other links and lift over

dbSNP: rs776437567; hg19: chr20-48431631;