3-112167328-A-T

Variant names:

• chr3-112167328-A-T
• NM_183061.3:c.3257T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_183061.3(SLC9C1):​c.3257T>A​(p.Phe1086Tyr) 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. 15/22 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. F1086L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC9C1 NM_183061.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22983128).

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.3257T>A	p.Phe1086Tyr	missense	Exon 26 of 29	NP_898884.1	Q4G0N8-1
	SLC9C1	NM_001320531.2		c.3113T>A	p.Phe1038Tyr	missense	Exon 25 of 28	NP_001307460.1	Q4G0N8-2
	SLC9C1	NR_135297.2		n.2527T>A		non_coding_transcript_exon	Exon 20 of 23

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9C1	ENST00000305815.10	TSL:2 MANE Select	c.3257T>A	p.Phe1086Tyr	missense	Exon 26 of 29	ENSP00000306627.5	Q4G0N8-1
	SLC9C1	ENST00000487372.5	TSL:1	c.3113T>A	p.Phe1038Tyr	missense	Exon 25 of 28	ENSP00000420688.1	Q4G0N8-2
	SLC9C1	ENST00000471295.1	TSL:5	n.*1586T>A		non_coding_transcript_exon	Exon 19 of 22	ENSP00000418371.1	F8WCJ0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.14
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.0082
Eigen_PC	Benign	0.043
FATHMM_MKL	Uncertain	0.76	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.4
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.20
Sift	Benign	0.053	T
Sift4G	Benign	0.14	T
Polyphen		0.47	P
Vest4		0.35
MutPred		0.25		Loss of ubiquitination at K1088 (P = 0.0816)
MVP		0.34
MPC		0.089
ClinPred		0.57	D
GERP RS		4.3
Varity_R		0.15
gMVP		0.23
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

hg19: chr3-111886175;