chr4-103044931-C-T

Position:

• chr4-103044931-C-T

Variant summary

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

The NM_178833.7(SLC9B2):​c.955G>A​(p.Val319Ile) 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. 15/21 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: SLC9B2 NM_178833.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0120

Genes affected

SLC9B2 (HGNC:25143): (solute carrier family 9 member B2) Sodium hydrogen antiporters, such as NHEDC2, convert the proton motive force established by the respiratory chain or the F1F0 mitochondrial ATPase into sodium gradients that drive other energy-requiring processes, transduce environmental signals into cell responses, or function in drug efflux (Xiang et al., 2007 [PubMed 18000046]).[supplied by OMIM, Mar 2008]

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=0.11941576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC9B2	NM_178833.7	c.955G>A	p.Val319Ile	missense_variant	8/12	ENST00000394785.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC9B2	ENST00000394785.9	c.955G>A	p.Val319Ile	missense_variant	8/12	2	NM_178833.7	P1

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

Mar 24, 2023

The c.955G>A (p.V319I) alteration is located in exon 8 (coding exon 7) of the SLC9B2 gene. This alteration results from a G to A substitution at nucleotide position 955, causing the valine (V) at amino acid position 319 to be replaced by an isoleucine (I). 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	0.063
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.3
DANN	Benign	0.62
DEOGEN2	Benign	0.026	T;.;T;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.040	N
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.10	N;.;N;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.010	N;N;N;N;N
REVEL	Benign	0.041
Sift	Benign	0.35	T;T;T;T;T
Sift4G	Benign	0.45	T;T;T;T;T
Polyphen		0.0040	B;.;B;B;B
Vest4		0.12
MutPred		0.63		Gain of catalytic residue at L320 (P = 0.4444);.;Gain of catalytic residue at L320 (P = 0.4444);.;.;
MVP		0.14
MPC		0.018
ClinPred		0.033	T
GERP RS		-2.4
Varity_R		0.049
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr4-103966088;