chr5-110568452-C-A

Variant summary

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

The NM_001039763.4(TMEM232):​c.1450G>T​(p.Ala484Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000647 in 1,544,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000065 ( 0 hom. )

Consequence

TMEM232
NM_001039763.4 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.45
Variant links:
Genes affected
TMEM232 (HGNC:37270): (transmembrane protein 232) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.3000861).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TMEM232NM_001039763.4 linkuse as main transcriptc.1450G>T p.Ala484Ser missense_variant 11/14 ENST00000455884.7 NP_001034852.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMEM232ENST00000455884.7 linkuse as main transcriptc.1450G>T p.Ala484Ser missense_variant 11/142 NM_001039763.4 ENSP00000401477 P1C9JQI7-1

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151858
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000646
AC:
9
AN:
1392632
Hom.:
0
Cov.:
30
AF XY:
0.00000582
AC XY:
4
AN XY:
686798
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:
0.0000203
Gnomad4 NFE exome
AF:
0.00000650
Gnomad4 OTH exome
AF:
0.0000173
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151858
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74154
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

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 30, 2021The c.1450G>T (p.A484S) alteration is located in exon 11 (coding exon 10) of the TMEM232 gene. This alteration results from a G to T substitution at nucleotide position 1450, causing the alanine (A) at amino acid position 484 to be replaced by a serine (S). 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
0.19
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.024
T
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Benign
0.70
T
M_CAP
Benign
0.0086
T
MetaRNN
Benign
0.30
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
2.0
M
MutationTaster
Benign
0.98
N;N
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.11
Sift
Benign
0.14
T
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.30
MutPred
0.35
Gain of disorder (P = 0.0531);
MVP
0.099
ClinPred
0.94
D
GERP RS
4.8
Varity_R
0.095
gMVP
0.072

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

LitVar

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

Other links and lift over

dbSNP: rs1364104586; hg19: chr5-109904153; API