3-112167328-A-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.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. 14/21 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)
• Consequence: SLC9C1 NM_183061.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40

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=0.22983128).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC9C1	NM_183061.3	c.3257T>A	p.Phe1086Tyr	missense_variant	26/29	ENST00000305815.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC9C1	ENST00000305815.10	c.3257T>A	p.Phe1086Tyr	missense_variant	26/29	2	NM_183061.3	P1
SLC9C1	ENST00000487372.5	c.3113T>A	p.Phe1038Tyr	missense_variant	25/28	1
SLC9C1	ENST00000471295.1	c.*1586T>A		3_prime_UTR_variant, NMD_transcript_variant	19/22	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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 22, 2023

The c.3257T>A (p.F1086Y) alteration is located in exon 26 (coding exon 25) of the SLC9C1 gene. This alteration results from a T to A substitution at nucleotide position 3257, causing the phenylalanine (F) at amino acid position 1086 to be replaced by a tyrosine (Y). 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	0.14
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;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.6	M;.
MutationTaster	Benign	0.98	N;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.20
Sift	Benign	0.053	T;T
Sift4G	Benign	0.14	T;T
Polyphen		0.47	P;B
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

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: chr3-111886175;