1-27100335-C-T

Variant names:

• chr1-27100335-C-T
• NM_003047.5:c.2420G>A

Variant summary

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

The NM_003047.5(SLC9A1):​c.2420G>A​(p.Gly807Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000144 in 1,384,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC9A1 NM_003047.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.79

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12857082).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A1	NM_003047.5	c.2420G>A	p.Gly807Glu	missense_variant	Exon 12 of 12	ENST00000263980.8	NP_003038.2
SLC9A1	XM_011542021.4	c.2090G>A	p.Gly697Glu	missense_variant	Exon 13 of 13		XP_011540323.1
SLC9A1	XM_047428769.1	c.2090G>A	p.Gly697Glu	missense_variant	Exon 16 of 16		XP_047284725.1
SLC9A1	NR_046474.2	n.2750G>A		non_coding_transcript_exon_variant	Exon 11 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A1	ENST00000263980.8	c.2420G>A	p.Gly807Glu	missense_variant	Exon 12 of 12	1	NM_003047.5	ENSP00000263980.3
SLC9A1	ENST00000374089.5	n.1645G>A		non_coding_transcript_exon_variant	Exon 7 of 7	2
SLC9A1	ENST00000447808.1	n.*10G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1384236 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 680338

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: 0.00000186

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2420G>A (p.G807E) alteration is located in exon 12 (coding exon 12) of the SLC9A1 gene. This alteration results from a G to A substitution at nucleotide position 2420, causing the glycine (G) at amino acid position 807 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.046
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.32	N
REVEL	Benign	0.064
Sift	Benign	0.51	T
Sift4G	Benign	1.0	T
Polyphen		0.27	B
Vest4		0.28
MutPred		0.20		Gain of solvent accessibility (P = 0.024);
MVP		0.17
MPC		0.96
ClinPred		0.80	D
GERP RS		4.6
Varity_R		0.056
gMVP		0.089

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-27426826;