rs371825629

Variant names:

• chrX-79361445-C-A
• rs371825629
• NM_004867.5:c.587G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-79361445-C-A
• chrX-79361445-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004867.5(ITM2A):​c.587G>T​(p.Arg196Leu) 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 pathogenic 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. R196Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 24)
• Consequence: ITM2A NM_004867.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.812

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004867.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITM2A	NM_004867.5	MANE Select	c.587G>T	p.Arg196Leu	missense	Exon 5 of 6	NP_004858.1	O43736-1
	ITM2A	NM_001171581.2		c.455G>T	p.Arg152Leu	missense	Exon 4 of 5	NP_001165052.1	O43736-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITM2A	ENST00000373298.7	TSL:1 MANE Select	c.587G>T	p.Arg196Leu	missense	Exon 5 of 6	ENSP00000362395.2	O43736-1
	ITM2A	ENST00000865381.1		c.587G>T	p.Arg196Leu	missense	Exon 6 of 7	ENSP00000535440.1
	ITM2A	ENST00000865383.1		c.587G>T	p.Arg196Leu	missense	Exon 6 of 7	ENSP00000535442.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	5.1
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.55
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.010	D
Sift4G	Benign	0.083	T
Polyphen		0.13	B
Vest4		0.54
MutPred		0.68		Gain of sheet (P = 0.1451)
MVP		0.67
MPC		0.36
ClinPred		0.96	D
GERP RS		0.53
Varity_R		0.27
gMVP		0.92
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs371825629; hg19: chrX-78616942;