NM_001170795.4:c.145G>C

Variant names:

• chr2-27213222-G-C
• rs764696052
• NM_001170795.4:c.145G>C

Variant summary

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

The NM_001170795.4(ATRAID):​c.145G>C​(p.Ala49Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATRAID NM_001170795.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.28
• Publications: 0 publications found

Genes affected

ATRAID (HGNC:24090): (all-trans retinoic acid induced differentiation factor) This gene is thought to be involved in apoptosis, and may also be involved in hematopoietic development and differentiation. The use of alternative splice sites and promotors result in multiple transcript variants encoding different isoforms.[provided by RefSeq, Dec 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATRAID	NM_001170795.4	c.145G>C	p.Ala49Pro	missense_variant	Exon 2 of 7	ENST00000380171.9	NP_001164266.1
ATRAID	NM_016085.5	c.-30G>C		5_prime_UTR_variant	Exon 2 of 7		NP_057169.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATRAID	ENST00000380171.9	c.145G>C	p.Ala49Pro	missense_variant	Exon 2 of 7	1	NM_001170795.4	ENSP00000369518.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 30, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.310G>C (p.A104P) alteration is located in exon 2 (coding exon 2) of the ATRAID gene. This alteration results from a G to C substitution at nucleotide position 310, causing the alanine (A) at amino acid position 104 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	.;.;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.65	.;T;T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.3	.;.;M
PhyloP100		2.3
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.6	D;.;.
REVEL	Benign	0.17
Sift	Benign	0.042	D;.;.
Sift4G	Benign	0.11	T;T;T
Polyphen		0.96	D;D;.
Vest4		0.64
MutPred		0.36		Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);.;
MVP		0.75
MPC		0.41
ClinPred		0.97	D
GERP RS		4.3
PromoterAI		-0.065	Neutral
Varity_R		0.13
gMVP		0.79
Mutation Taster		=66/34	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs764696052; hg19: chr2-27436090;