X-79361426-C-T

Variant names:

• chrX-79361426-C-T
• rs138551324
• NM_004867.5:c.606G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_004867.5(ITM2A):​c.606G>A​(p.Val202Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00861 in 1,205,178 control chromosomes in the GnomAD database, including 37 homozygotes. There are 3,257 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0062 (2 hom., 191 hem., cov: 23)
  • Exomes 𝑓: 0.0089 (35 hom. 3066 hem.)
• Consequence: ITM2A NM_004867.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.28
• 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant X-79361426-C-T is Benign according to our data. Variant chrX-79361426-C-T is described in ClinVar as Benign. ClinVar VariationId is 769489.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.28 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 gene

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.606G>A	p.Val202Val	synonymous	Exon 5 of 6	NP_004858.1	O43736-1
	ITM2A	NM_001171581.2		c.474G>A	p.Val158Val	synonymous	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.606G>A	p.Val202Val	synonymous	Exon 5 of 6	ENSP00000362395.2	O43736-1
	ITM2A	ENST00000865381.1		c.606G>A	p.Val202Val	synonymous	Exon 6 of 7	ENSP00000535440.1
	ITM2A	ENST00000865383.1		c.606G>A	p.Val202Val	synonymous	Exon 6 of 7	ENSP00000535442.1

Frequencies

GnomAD3 genomes AF: 0.00623 AC: 700 AN: 112304 Hom.: 2 Cov.: 23

Gnomad AFR AF: 0.00129

Gnomad AMI AF: 0.00146

Gnomad AMR AF: 0.00424

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00255

Gnomad FIN AF: 0.00376

Gnomad MID AF: 0.00833

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.00591

GnomAD2 exomes AF: 0.00662 AC: 1208 AN: 182401 AF XY: 0.00663

Gnomad AFR exome AF: 0.00122

Gnomad AMR exome AF: 0.00475

Gnomad ASJ exome AF: 0.0121

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00400

Gnomad NFE exome AF: 0.00987

Gnomad OTH exome AF: 0.00491

GnomAD4 exome AF: 0.00886 AC: 9682 AN: 1092821 Hom.: 35 Cov.: 28 AF XY: 0.00855 AC XY: 3066 AN XY: 358457

African (AFR) AF: 0.00110 AC: 29 AN: 26288

American (AMR) AF: 0.00487 AC: 171 AN: 35126

Ashkenazi Jewish (ASJ) AF: 0.0132 AC: 256 AN: 19327

East Asian (EAS) AF: 0.00 AC: 0 AN: 30165

South Asian (SAS) AF: 0.00494 AC: 266 AN: 53895

European-Finnish (FIN) AF: 0.00360 AC: 146 AN: 40517

Middle Eastern (MID) AF: 0.00388 AC: 16 AN: 4124

European-Non Finnish (NFE) AF: 0.0101 AC: 8459 AN: 837445

Other (OTH) AF: 0.00738 AC: 339 AN: 45934

GnomAD4 genome AF: 0.00623 AC: 700 AN: 112357 Hom.: 2 Cov.: 23 AF XY: 0.00552 AC XY: 191 AN XY: 34571

African (AFR) AF: 0.00129 AC: 40 AN: 31013

American (AMR) AF: 0.00423 AC: 45 AN: 10637

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 32 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3586

South Asian (SAS) AF: 0.00256 AC: 7 AN: 2733

European-Finnish (FIN) AF: 0.00376 AC: 23 AN: 6116

Middle Eastern (MID) AF: 0.00913 AC: 2 AN: 219

European-Non Finnish (NFE) AF: 0.0102 AC: 541 AN: 53177

Other (OTH) AF: 0.00584 AC: 9 AN: 1541

Alfa AF: 0.00824 Hom.: 60

Bravo AF: 0.00619

EpiCase AF: 0.0119

EpiControl AF: 0.0116

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.3
DANN	Benign	0.59
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs138551324; hg19: chrX-78616923;