4-103026566-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_178833.7(SLC9B2):​c.1418A>G​(p.Asp473Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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

Scores

5
9
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.19
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.852

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC9B2NM_178833.7 linkuse as main transcriptc.1418A>G p.Asp473Gly missense_variant 12/12 ENST00000394785.9 NP_849155.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC9B2ENST00000394785.9 linkuse as main transcriptc.1418A>G p.Asp473Gly missense_variant 12/122 NM_178833.7 ENSP00000378265 P1Q86UD5-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 22, 2024The c.1418A>G (p.D473G) alteration is located in exon 12 (coding exon 11) of the SLC9B2 gene. This alteration results from a A to G substitution at nucleotide position 1418, causing the aspartic acid (D) at amino acid position 473 to be replaced by a glycine (G). 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
0.74
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.080
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
T;T;.
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.60
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
.;D;D
M_CAP
Benign
0.031
D
MetaRNN
Pathogenic
0.85
D;D;D
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.64
T
PROVEAN
Pathogenic
-4.4
D;D;D
REVEL
Uncertain
0.53
Sift
Uncertain
0.0030
D;D;D
Sift4G
Uncertain
0.018
D;D;D
Polyphen
1.0
D;D;P
Vest4
0.94
MutPred
0.59
Gain of methylation at R476 (P = 0.0566);Gain of methylation at R476 (P = 0.0566);.;
MVP
0.58
MPC
0.16
ClinPred
0.99
D
GERP RS
5.2
Varity_R
0.89
gMVP
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.19
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1742234194; hg19: chr4-103947723; API