rs3180834

Variant names:

• chrX-79361355-C-G
• rs3180834
• NM_004867.5:c.677G>C

Your query was ambiguous. Multiple possible variants found:

• chrX-79361355-C-G
• chrX-79361355-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004867.5(ITM2A):​c.677G>C​(p.Arg226Pro) 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.

• Frequency: Genomes: not found (cov: 24)
• Consequence: ITM2A NM_004867.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.799

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITM2A	NM_004867.5	c.677G>C	p.Arg226Pro	missense_variant	Exon 5 of 6	ENST00000373298.7	NP_004858.1
ITM2A	NM_001171581.2	c.545G>C	p.Arg182Pro	missense_variant	Exon 4 of 5		NP_001165052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITM2A	ENST00000373298.7	c.677G>C	p.Arg226Pro	missense_variant	Exon 5 of 6	1	NM_004867.5	ENSP00000362395.2
ITM2A	ENST00000434584.2	c.545G>C	p.Arg182Pro	missense_variant	Exon 4 of 5	2		ENSP00000415533.2
ITM2A	ENST00000469541.5	n.637G>C		non_coding_transcript_exon_variant	Exon 5 of 6	2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;.
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.81	T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Uncertain	0.35	D
MutationAssessor	Benign	1.9	L;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-4.9	D;D
REVEL	Pathogenic	0.68
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.98	D;.
Vest4		0.65
MutPred		0.67		Loss of MoRF binding (P = 6e-04);.;
MVP		0.83
MPC		0.72
ClinPred		0.99	D
GERP RS		4.1
Varity_R		0.91
gMVP		1.0

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

LitVar

Other links and lift over

dbSNP: rs3180834; hg19: chrX-78616852;