chrX-79363120-T-A

Variant names:

• chrX-79363120-T-A
• rs1329389687
• NM_004867.5:c.263A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004867.5(ITM2A):​c.263A>T​(p.Glu88Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000915 in 1,093,181 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. 14/21 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: 9.1e-7 (0 hom. 0 hem.)
• Consequence: ITM2A NM_004867.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.75
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23377949).

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.263A>T	p.Glu88Val	missense	Exon 3 of 6	NP_004858.1	O43736-1
	ITM2A	NM_001171581.2		c.131A>T	p.Glu44Val	missense	Exon 2 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.263A>T	p.Glu88Val	missense	Exon 3 of 6	ENSP00000362395.2	O43736-1
	ITM2A	ENST00000865381.1		c.263A>T	p.Glu88Val	missense	Exon 4 of 7	ENSP00000535440.1
	ITM2A	ENST00000865383.1		c.263A>T	p.Glu88Val	missense	Exon 4 of 7	ENSP00000535442.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.15e-7 AC: 1 AN: 1093181 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 358901

African (AFR) AF: 0.00 AC: 0 AN: 26336

American (AMR) AF: 0.00 AC: 0 AN: 34828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19292

East Asian (EAS) AF: 0.00 AC: 0 AN: 30141

South Asian (SAS) AF: 0.00 AC: 0 AN: 53385

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40385

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4116

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 838758

Other (OTH) AF: 0.00 AC: 0 AN: 45940

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.028	T
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.84	L
PhyloP100		2.7
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.082
Sift	Benign	0.64	T
Sift4G	Benign	0.24	T
Polyphen		0.029	B
Vest4		0.58
MutPred		0.43		Loss of disorder (P = 0.125)
MVP		0.18
MPC		0.17
ClinPred		0.74	D
GERP RS		4.3
Varity_R		0.17
gMVP		0.67
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1329389687; hg19: chrX-78618617;