rs778721211

Variant names:

• chr16-67249055-C-A
• rs778721211
• NM_004594.3:c.41C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-67249055-C-A
• chr16-67249055-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004594.3(SLC9A5):​c.41C>A​(p.Ala14Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 1,354,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 0.0000015 (0 hom.)
• Consequence: SLC9A5 NM_004594.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.648

Genes affected

SLC9A5 (HGNC:11078): (solute carrier family 9 member A5) Predicted to enable potassium:proton antiporter activity and sodium:proton antiporter activity. Predicted to be involved in potassium ion transmembrane transport; regulation of intracellular pH; and sodium ion import across plasma membrane. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. Implicated in end stage renal disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08332986).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A5	NM_004594.3	c.41C>A	p.Ala14Glu	missense_variant	Exon 1 of 16	ENST00000299798.16	NP_004585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A5	ENST00000299798.16	c.41C>A	p.Ala14Glu	missense_variant	Exon 1 of 16	1	NM_004594.3	ENSP00000299798.11

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000864 AC: 1 AN: 115722 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 64080

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000493

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000148 AC: 2 AN: 1354766 Hom.: 0 Cov.: 31 AF XY: 0.00000149 AC XY: 1 AN XY: 669402

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: 0.0000261

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	0.17
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.43	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.15
Sift	Benign	0.33	T
Sift4G	Benign	0.36	T
Polyphen		0.0070	B
Vest4		0.070
MutPred		0.17		Loss of MoRF binding (P = 0.2378);
MVP		0.71
MPC		0.68
ClinPred		0.14	T
GERP RS		3.9
Varity_R		0.11
gMVP		0.53

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: rs778721211; hg19: chr16-67282958;