X-79361094-C-T

Variant names:

• chrX-79361094-C-T
• NM_004867.5:c.787G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004867.5(ITM2A):​c.787G>A​(p.Glu263Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: ITM2A NM_004867.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.11

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]

ACMG classification

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=0.12222943).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITM2A	NM_004867.5	c.787G>A	p.Glu263Lys	missense_variant	Exon 6 of 6	ENST00000373298.7	NP_004858.1
ITM2A	NM_001171581.2	c.655G>A	p.Glu219Lys	missense_variant	Exon 5 of 5		NP_001165052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITM2A	ENST00000373298.7	c.787G>A	p.Glu263Lys	missense_variant	Exon 6 of 6	1	NM_004867.5	ENSP00000362395.2
ITM2A	ENST00000434584.2	c.655G>A	p.Glu219Lys	missense_variant	Exon 5 of 5	2		ENSP00000415533.2
ITM2A	ENST00000469541.5	n.747G>A		non_coding_transcript_exon_variant	Exon 6 of 6	2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 22

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.787G>A (p.E263K) alteration is located in exon 6 (coding exon 6) of the ITM2A gene. This alteration results from a G to A substitution at nucleotide position 787, causing the glutamic acid (E) at amino acid position 263 to be replaced by a lysine (K). 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	0.21
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T;.
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.47	N;N
REVEL	Benign	0.032
Sift	Uncertain	0.019	D;T
Sift4G	Benign	0.21	T;T
Polyphen		0.48	P;.
Vest4		0.16
MutPred		0.28		Gain of methylation at E263 (P = 0.0028);.;
MVP		0.22
MPC		0.28
ClinPred		0.55	D
GERP RS		3.6
Varity_R		0.19
gMVP		0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chrX-78616591;