4-103028859-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178833.7(SLC9B2):ā€‹c.1280T>Cā€‹(p.Ile427Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,603,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.00011 ( 0 hom. )

Consequence

SLC9B2
NM_178833.7 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22340697).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC9B2NM_178833.7 linkuse as main transcriptc.1280T>C p.Ile427Thr missense_variant 11/12 ENST00000394785.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC9B2ENST00000394785.9 linkuse as main transcriptc.1280T>C p.Ile427Thr missense_variant 11/122 NM_178833.7 P1Q86UD5-1

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152162
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000419
AC:
10
AN:
238802
Hom.:
0
AF XY:
0.0000462
AC XY:
6
AN XY:
129734
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000909
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000111
AC:
161
AN:
1450954
Hom.:
0
Cov.:
30
AF XY:
0.000112
AC XY:
81
AN XY:
721762
show subpopulations
Gnomad4 AFR exome
AF:
0.0000307
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000119
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000132
Gnomad4 OTH exome
AF:
0.000217
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152162
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000148
Hom.:
0
Bravo
AF:
0.0000831
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.0000247
AC:
3

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 GeneticsAug 08, 2023The c.1280T>C (p.I427T) alteration is located in exon 11 (coding exon 10) of the SLC9B2 gene. This alteration results from a T to C substitution at nucleotide position 1280, causing the isoleucine (I) at amino acid position 427 to be replaced by a threonine (T). 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
0.073
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
15
DANN
Benign
0.97
DEOGEN2
Benign
0.097
T;T;.
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.42
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.32
.;T;T
M_CAP
Benign
0.0091
T
MetaRNN
Benign
0.22
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.7
L;L;.
MutationTaster
Benign
0.99
D;D;D;D;D
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-2.7
D;D;N
REVEL
Benign
0.062
Sift
Benign
0.054
T;T;D
Sift4G
Uncertain
0.019
D;D;D
Polyphen
0.55
P;P;P
Vest4
0.45
MVP
0.23
MPC
0.021
ClinPred
0.82
D
GERP RS
-0.10
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.15
gMVP
0.56

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
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: rs147533176; hg19: chr4-103950016; API