rs770079462

Variant names:

• chrX-79363078-C-A
• NM_004867.5:c.305G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-79363078-C-A
• chrX-79363078-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004867.5(ITM2A):​c.305G>T​(p.Arg102Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,312 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R102H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: ITM2A NM_004867.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052758873).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITM2A	NM_004867.5	c.305G>T	p.Arg102Leu	missense_variant	Exon 3 of 6	ENST00000373298.7	NP_004858.1
ITM2A	NM_001171581.2	c.173G>T	p.Arg58Leu	missense_variant	Exon 2 of 5		NP_001165052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITM2A	ENST00000373298.7	c.305G>T	p.Arg102Leu	missense_variant	Exon 3 of 6	1	NM_004867.5	ENSP00000362395.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1096312 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 361784

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: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.96
DANN	Benign	0.48
DEOGEN2	Benign	0.011	T;.
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.053	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.090	N;N
REVEL	Benign	0.023
Sift	Benign	0.66	T;T
Sift4G	Benign	0.76	T;T
Polyphen		0.0	B;.
Vest4		0.20
MutPred		0.30		Loss of solvent accessibility (P = 0.0052);.;
MVP		0.043
MPC		0.17
ClinPred		0.025	T
GERP RS		-7.1
Varity_R		0.059
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-78618575;