3-112151959-C-T

Variant summary

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

The NM_183061.3(SLC9C1):c.3422G>A(p.Gly1141Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SLC9C1 NM_183061.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.237

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

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=0.13943553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC9C1	NM_183061.3	c.3422G>A	p.Gly1141Glu	missense_variant	28/29	ENST00000305815.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC9C1	ENST00000305815.10	c.3422G>A	p.Gly1141Glu	missense_variant	28/29	2	NM_183061.3	P1
SLC9C1	ENST00000487372.5	c.3278G>A	p.Gly1093Glu	missense_variant	27/28	1
SLC9C1	ENST00000471295.1	c.*1751G>A		3_prime_UTR_variant, NMD_transcript_variant	21/22	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436830 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 714598

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: 9.05e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2021

The c.3422G>A (p.G1141E) alteration is located in exon 28 (coding exon 27) of the SLC9C1 gene. This alteration results from a G to A substitution at nucleotide position 3422, causing the glycine (G) at amino acid position 1141 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	0.072
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	1.1
Dann	Uncertain	0.98
DEOGEN2	Benign	0.020	T;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.050	N
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.55	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.33	N;N
REVEL	Benign	0.20
Sift	Benign	0.068	T;T
Sift4G	Benign	0.064	T;T
Polyphen		0.90	P;P
Vest4		0.15
MutPred		0.21		Gain of helix (P = 0.0078);.;
MVP		0.68
MPC		0.072
ClinPred		0.37	T
GERP RS		2.2
Varity_R		0.067
gMVP		0.034

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: chr3-111870806;