chr4-103047158-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_178833.7(SLC9B2):​c.782A>T​(p.Tyr261Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SLC9B2
NM_178833.7 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.31
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.42156923).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC9B2NM_178833.7 linkuse as main transcriptc.782A>T p.Tyr261Phe missense_variant 7/12 ENST00000394785.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC9B2ENST00000394785.9 linkuse as main transcriptc.782A>T p.Tyr261Phe missense_variant 7/122 NM_178833.7 P1Q86UD5-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461676
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727124
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00
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 GeneticsMay 20, 2024The c.782A>T (p.Y261F) alteration is located in exon 7 (coding exon 6) of the SLC9B2 gene. This alteration results from a A to T substitution at nucleotide position 782, causing the tyrosine (Y) at amino acid position 261 to be replaced by a phenylalanine (F). 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
0.10
BayesDel_addAF
Benign
-0.090
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.22
T;.;T;T;.
Eigen
Uncertain
0.22
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.91
.;D;D;D;D
M_CAP
Benign
0.0052
T
MetaRNN
Benign
0.42
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.5
M;.;M;.;.
MutationTaster
Benign
0.99
D;D;D;D;D
PrimateAI
Uncertain
0.61
T
PROVEAN
Uncertain
-3.2
D;D;D;D;D
REVEL
Benign
0.13
Sift
Benign
0.062
T;D;T;D;T
Sift4G
Benign
0.13
T;T;T;T;T
Polyphen
0.18
B;.;B;P;B
Vest4
0.50
MutPred
0.62
Loss of methylation at K265 (P = 0.0527);.;Loss of methylation at K265 (P = 0.0527);.;.;
MVP
0.12
MPC
0.037
ClinPred
0.93
D
GERP RS
5.9
Varity_R
0.31
gMVP
0.51

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: chr4-103968315; API