Variant chrX-79367193-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004867.5(ITM2A):c.23C>A(p.Thr8Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000823 in 1,092,910 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000082 ( 0 hom. 2 hem. )

Consequence

ITM2A
NM_004867.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.63

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]

ITM2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13239464).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITM2A	NM_004867.5 linkuse as main transcript	c.23C>A	p.Thr8Asn	missense_variant	1/6	ENST00000373298.7
ITM2A	NM_001171581.2 linkuse as main transcript	c.23C>A	p.Thr8Asn	missense_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITM2A	ENST00000373298.7 linkuse as main transcript	c.23C>A	p.Thr8Asn	missense_variant	1/6	1	NM_004867.5	P1	O43736-1
ITM2A	ENST00000434584.2 linkuse as main transcript	c.23C>A	p.Thr8Asn	missense_variant	1/5	2			O43736-2
ITM2A	ENST00000461357.1 linkuse as main transcript	n.202C>A		non_coding_transcript_exon_variant	2/2	5
ITM2A	ENST00000482194.1 linkuse as main transcript	n.126C>A		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000284

AC:

AN:

176209

Hom.:

AF XY:

0.0000163

AC XY:

AN XY:

61309

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000373

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000823

AC:

AN:

1092910

Hom.:

Cov.:

AF XY:

0.00000558

AC XY:

AN XY:

358464

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000299

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

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 submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.23C>A (p.T8N) alteration is located in exon 1 (coding exon 1) of the ITM2A gene. This alteration results from a C to A substitution at nucleotide position 23, causing the threonine (T) at amino acid position 8 to be replaced by an asparagine (N). 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

0.12

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.023

T;.

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.86

D;T

M_CAP

Benign

0.038

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

0.79

D;D

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.80

N;N

REVEL

Benign

0.083

Sift

Uncertain

0.0080

D;D

Sift4G

Uncertain

0.022

D;T

Polyphen

0.84

P;.

Vest4

0.29

MutPred

0.34

Loss of phosphorylation at T8 (P = 0.0518);Loss of phosphorylation at T8 (P = 0.0518);

MVP

0.35

MPC

0.22

ClinPred

0.14

GERP RS

4.1

Varity_R

0.32

gMVP

0.63

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over