chr3-112202269-C-G

Position:

• chr3-112202269-C-G

Variant summary

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

The NM_183061.3(SLC9C1):​c.2303G>C​(p.Ser768Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S768I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC9C1 NM_183061.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121

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]

SLC9C1 (HGNC:):

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=0.06870365).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9C1	NM_183061.3	c.2303G>C	p.Ser768Thr	missense_variant	18/29	ENST00000305815.10	NP_898884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC9C1	ENST00000305815.10	c.2303G>C	p.Ser768Thr	missense_variant	18/29	2	NM_183061.3	ENSP00000306627.5
SLC9C1	ENST00000487372.5	c.2159G>C	p.Ser720Thr	missense_variant	17/28	1		ENSP00000420688.1
SLC9C1	ENST00000471295.1	n.*632G>C		non_coding_transcript_exon_variant	11/22	5		ENSP00000418371.1
SLC9C1	ENST00000471295.1	n.*632G>C		3_prime_UTR_variant	11/22	5		ENSP00000418371.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.89
DEOGEN2	Benign	0.11	T;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.63	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.069	T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.3	L;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.13
Sift	Benign	0.67	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.013	B;B
Vest4		0.064
MutPred		0.16		Loss of loop (P = 0.0374);.;
MVP		0.43
MPC		0.057
ClinPred		0.21	T
GERP RS		2.0
Varity_R		0.058
gMVP		0.18

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: rs9288938; hg19: chr3-111921116;