NM_004867.5:c.442-10T>C

Variant names:

• chrX-79362701-A-G
• rs184180205
• NM_004867.5:c.442-10T>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_004867.5(ITM2A):​c.442-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00065 in 1,120,976 control chromosomes in the GnomAD database, including 4 homozygotes. There are 196 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (1 hom., 106 hem., cov: 22)
  • Exomes 𝑓: 0.00039 (3 hom. 90 hem.)
• Consequence: ITM2A NM_004867.5 intron
• Scores: Splicing: ADA: 0.0002121
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.54
• 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant X-79362701-A-G is Benign according to our data. Variant chrX-79362701-A-G is described in ClinVar as [Benign]. Clinvar id is 714929.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Hemizygotes in GnomAd4 at 106 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITM2A	NM_004867.5	c.442-10T>C		intron_variant	Intron 3 of 5	ENST00000373298.7	NP_004858.1
ITM2A	NM_001171581.2	c.310-10T>C		intron_variant	Intron 2 of 4		NP_001165052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITM2A	ENST00000373298.7	c.442-10T>C		intron_variant	Intron 3 of 5	1	NM_004867.5	ENSP00000362395.2
ITM2A	ENST00000434584.2	c.310-10T>C		intron_variant	Intron 2 of 4	2		ENSP00000415533.2
ITM2A	ENST00000469541.5	n.402-10T>C		intron_variant	Intron 3 of 5	2
ITM2A	ENST00000482194.1	n.413-10T>C		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.00306 AC: 340 AN: 111101 Hom.: 1 Cov.: 22

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00106

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000754

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00111 AC: 187 AN: 167723 AF XY: 0.000808

Gnomad AFR exome AF: 0.0126

Gnomad AMR exome AF: 0.000558

Gnomad ASJ exome AF: 0.000156

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000909

Gnomad OTH exome AF: 0.000488

GnomAD4 exome AF: 0.000385 AC: 389 AN: 1009823 Hom.: 3 Cov.: 21 AF XY: 0.000311 AC XY: 90 AN XY: 289831

African (AFR) AF: 0.0121 AC: 295 AN: 24407

American (AMR) AF: 0.000782 AC: 25 AN: 31973

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18214

East Asian (EAS) AF: 0.00 AC: 0 AN: 29878

South Asian (SAS) AF: 0.000202 AC: 10 AN: 49513

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40344

Middle Eastern (MID) AF: 0.000257 AC: 1 AN: 3884

European-Non Finnish (NFE) AF: 0.0000208 AC: 16 AN: 768441

Other (OTH) AF: 0.000973 AC: 42 AN: 43169

GnomAD4 genome AF: 0.00306 AC: 340 AN: 111153 Hom.: 1 Cov.: 22 AF XY: 0.00318 AC XY: 106 AN XY: 33351

African (AFR) AF: 0.0106 AC: 325 AN: 30595

American (AMR) AF: 0.00106 AC: 11 AN: 10398

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2629

East Asian (EAS) AF: 0.00 AC: 0 AN: 3535

South Asian (SAS) AF: 0.00 AC: 0 AN: 2647

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5922

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.0000754 AC: 4 AN: 53016

Other (OTH) AF: 0.00 AC: 0 AN: 1509

Alfa AF: 0.00139 Hom.: 5

Bravo AF: 0.00428

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.9
DANN	Benign	0.49
PhyloP100		2.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00021
dbscSNV1_RF	Benign	0.052
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: rs184180205; hg19: chrX-78618198;