rs779331823

Variant names:

• chr3-112151959-C-A
• rs779331823
• NM_183061.3:c.3422G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-112151959-C-A
• chr3-112151959-C-T
• chr3-112151959-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_183061.3(SLC9C1):​c.3422G>T​(p.Gly1141Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1141E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC9C1 NM_183061.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.237
• Publications: 0 publications found

Genes affected

SLC9C1 (HGNC:31401): (solute carrier family 9 member C1) 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 act upstream of or within flagellated sperm motility. Predicted to be located in motile cilium. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183061.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9C1	NM_183061.3	MANE Select	c.3422G>T	p.Gly1141Val	missense	Exon 28 of 29	NP_898884.1	Q4G0N8-1
	SLC9C1	NM_001320531.2		c.3278G>T	p.Gly1093Val	missense	Exon 27 of 28	NP_001307460.1	Q4G0N8-2
	SLC9C1	NR_135297.2		n.2692G>T		non_coding_transcript_exon	Exon 22 of 23

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9C1	ENST00000305815.10	TSL:2 MANE Select	c.3422G>T	p.Gly1141Val	missense	Exon 28 of 29	ENSP00000306627.5	Q4G0N8-1
	SLC9C1	ENST00000487372.5	TSL:1	c.3278G>T	p.Gly1093Val	missense	Exon 27 of 28	ENSP00000420688.1	Q4G0N8-2
	SLC9C1	ENST00000471295.1	TSL:5	n.*1751G>T		non_coding_transcript_exon	Exon 21 of 22	ENSP00000418371.1	F8WCJ0

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1436830 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 714598

African (AFR) AF: 0.00 AC: 0 AN: 31670

American (AMR) AF: 0.00 AC: 0 AN: 37176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25046

East Asian (EAS) AF: 0.00 AC: 0 AN: 38818

South Asian (SAS) AF: 0.00 AC: 0 AN: 81242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5368

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105000

Other (OTH) AF: 0.00 AC: 0 AN: 59340

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74334

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	4.8
DANN	Benign	0.96
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.095	N
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.24
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.21
Sift	Benign	0.076	T
Sift4G	Uncertain	0.052	T
Polyphen		0.95	P
Vest4		0.16
MutPred		0.20		Loss of loop (P = 0.0112)
MVP		0.76
MPC		0.068
ClinPred		0.37	T
GERP RS		2.2
Varity_R		0.077
gMVP		0.061
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.23		Position offset: 4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs779331823; hg19: chr3-111870806;