X-79363126-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004867.5(ITM2A):​c.257G>A​(p.Arg86His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000183 in 1,090,926 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 22)
Exomes 𝑓: 0.000018 ( 0 hom. 5 hem. )

Consequence

ITM2A
NM_004867.5 missense

Scores

17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.27
Variant links:
Genes affected
ITM2A (HGNC:6173): (integral membrane protein 2A) This gene encodes a type II membrane protein that belongs to the ITM2 family. Studies in mouse suggest that it may be involved in osteo- and chondrogenic differentiation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.033008575).
BP6
Variant X-79363126-C-T is Benign according to our data. Variant chrX-79363126-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3530800.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ITM2ANM_004867.5 linkc.257G>A p.Arg86His missense_variant Exon 3 of 6 ENST00000373298.7 NP_004858.1 O43736-1
ITM2ANM_001171581.2 linkc.125G>A p.Arg42His missense_variant Exon 2 of 5 NP_001165052.1 O43736-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ITM2AENST00000373298.7 linkc.257G>A p.Arg86His missense_variant Exon 3 of 6 1 NM_004867.5 ENSP00000362395.2 O43736-1

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD3 exomes
AF:
0.0000520
AC:
9
AN:
173069
Hom.:
0
AF XY:
0.0000340
AC XY:
2
AN XY:
58739
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000188
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000569
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000396
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000183
AC:
20
AN:
1090926
Hom.:
0
Cov.:
29
AF XY:
0.0000140
AC XY:
5
AN XY:
356838
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000173
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000376
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000131
Gnomad4 OTH exome
AF:
0.0000218
GnomAD4 genome
Cov.:
22
Bravo
AF:
0.0000718
ExAC
AF:
0.0000578
AC:
7

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Sep 30, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.059
BayesDel_addAF
Benign
-0.61
T
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.29
DANN
Benign
0.27
DEOGEN2
Benign
0.014
T;.
FATHMM_MKL
Benign
0.028
N
LIST_S2
Benign
0.84
T;T
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.033
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.93
N;.
PrimateAI
Benign
0.29
T
PROVEAN
Benign
0.89
N;N
REVEL
Benign
0.076
Sift
Benign
1.0
T;T
Sift4G
Benign
0.65
T;T
Polyphen
0.0
B;.
Vest4
0.081
MutPred
0.55
Gain of glycosylation at T83 (P = 0.0755);.;
MVP
0.11
MPC
0.17
ClinPred
0.014
T
GERP RS
-1.7
Varity_R
0.032
gMVP
0.46

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: rs753512845; hg19: chrX-78618623; API