1-27100436-T-G

Position:

• chr1-27100436-T-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_003047.5(SLC9A1):​c.2319A>C​(p.Gly773Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00049 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC9A1 NM_003047.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.314

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]

SLC9A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 1-27100436-T-G is Benign according to our data. Variant chr1-27100436-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2638552.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.314 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9A1	NM_003047.5	c.2319A>C	p.Gly773Gly	synonymous_variant	12/12	ENST00000263980.8	NP_003038.2
SLC9A1	XM_011542021.4	c.1989A>C	p.Gly663Gly	synonymous_variant	13/13		XP_011540323.1
SLC9A1	XM_047428769.1	c.1989A>C	p.Gly663Gly	synonymous_variant	16/16		XP_047284725.1
SLC9A1	NR_046474.2	n.2649A>C		non_coding_transcript_exon_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC9A1	ENST00000263980.8	c.2319A>C	p.Gly773Gly	synonymous_variant	12/12	1	NM_003047.5	ENSP00000263980.3
SLC9A1	ENST00000374089.5	n.1544A>C		non_coding_transcript_exon_variant	7/7	2
SLC9A1	ENST00000447808.1	n.796A>C		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 18 AN: 151982 Hom.: 0 Cov.: 34 FAILED QC

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.000831

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000883

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000492 AC: 711 AN: 1444750 Hom.: 0 Cov.: 38 AF XY: 0.000467 AC XY: 336 AN XY: 719196

Gnomad4 AFR exome AF: 0.000181

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.000193

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000175

Gnomad4 FIN exome AF: 0.0000751

Gnomad4 NFE exome AF: 0.000591

Gnomad4 OTH exome AF: 0.000468

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000118 AC: 18 AN: 152098 Hom.: 0 Cov.: 34 AF XY: 0.000134 AC XY: 10 AN XY: 74372

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000389

Gnomad4 SAS AF: 0.000832

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.0000883

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

SLC9A1: BP4, BP7 -

SLC9A1-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 21, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.1
DANN	Benign	0.55

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: rs2083133359; hg19: chr1-27426927;