chr4-103048978-C-G

Position:

• chr4-103048978-C-G

Variant summary

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

The NM_178833.7(SLC9B2):​c.628G>C​(p.Gly210Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 2.58

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC9B2	NM_178833.7	c.628G>C	p.Gly210Arg	missense_variant	6/12	ENST00000394785.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC9B2	ENST00000394785.9	c.628G>C	p.Gly210Arg	missense_variant	6/12	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 26, 2024

The c.628G>C (p.G210R) alteration is located in exon 6 (coding exon 5) of the SLC9B2 gene. This alteration results from a G to C substitution at nucleotide position 628, causing the glycine (G) at amino acid position 210 to be replaced by an arginine (R). 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	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.29	T;.;T;T;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.98	.;D;D;D;D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.66	D;D;D;D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.9	M;.;M;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-5.1	D;D;D;D;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.027	D;D;D;D;T
Sift4G	Benign	0.29	T;T;T;T;T
Polyphen		1.0	D;.;D;D;D
Vest4		0.86
MutPred		0.65		Gain of methylation at G210 (P = 0.0178);.;Gain of methylation at G210 (P = 0.0178);.;.;
MVP		0.46
MPC		0.16
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.81
gMVP		0.93

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: chr4-103970135;