rs797044991

Variant names:

• chr1-27105979-G-A
• rs797044991
• NM_003047.5:c.1391C>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003047.5(SLC9A1):​c.1391C>T​(p.Ser464Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC9A1 NM_003047.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 8.15

Genes affected

SLC9A1 (HGNC:11071): (solute carrier family 9 member A1) This gene encodes a Na+/H+ antiporter that is a member of the solute carrier family 9. The encoded protein is a plasma membrane transporter that is expressed in the kidney and intestine. This protein plays a central role in regulating pH homeostasis, cell migration and cell volume. This protein may also be involved in tumor growth. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.789

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A1	NM_003047.5	c.1391C>T	p.Ser464Phe	missense_variant	Exon 5 of 12	ENST00000263980.8	NP_003038.2
SLC9A1	XM_011542021.4	c.1061C>T	p.Ser354Phe	missense_variant	Exon 6 of 13		XP_011540323.1
SLC9A1	XM_047428769.1	c.1061C>T	p.Ser354Phe	missense_variant	Exon 9 of 16		XP_047284725.1
SLC9A1	NR_046474.2	n.1721C>T		non_coding_transcript_exon_variant	Exon 4 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A1	ENST00000263980.8	c.1391C>T	p.Ser464Phe	missense_variant	Exon 5 of 12	1	NM_003047.5	ENSP00000263980.3
SLC9A1	ENST00000374086.3	c.1391C>T	p.Ser464Phe	missense_variant	Exon 5 of 5	1		ENSP00000363199.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Jan 15, 2015

OMIM

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;.
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-4.9	D;D
REVEL	Uncertain	0.63
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;D
Vest4		0.72
MutPred		0.80		Loss of catalytic residue at S464 (P = 0.1636);Loss of catalytic residue at S464 (P = 0.1636);
MVP		0.51
MPC		1.3
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.89
gMVP		0.99

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: rs797044991; hg19: chr1-27432470;