3-48446930-C-G

Variant names:

• chr3-48446930-C-G
• rs530772573
• NM_130384.3:c.85C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_130384.3(ATRIP):​c.85C>G​(p.Pro29Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000461 in 1,302,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: ATRIP NM_130384.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.18

Genes affected

ATRIP (HGNC:33499): (ATR interacting protein) This gene encodes an essential component of the DNA damage checkpoint. The encoded protein binds to single-stranded DNA coated with replication protein A. The protein also interacts with the ataxia telangiectasia and Rad3 related protein kinase, resulting in its accumulation at intranuclear foci induced by DNA damage. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2012]

ATRIP-TREX1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29097527).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATRIP	NM_130384.3	c.85C>G	p.Pro29Ala	missense_variant	Exon 1 of 13	ENST00000320211.10	NP_569055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATRIP	ENST00000320211.10	c.85C>G	p.Pro29Ala	missense_variant	Exon 1 of 13	1	NM_130384.3	ENSP00000323099.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000461 AC: 6 AN: 1302080 Hom.: 0 Cov.: 31 AF XY: 0.00000779 AC XY: 5 AN XY: 641952

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000622

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000193

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 11, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.85C>G (p.P29A) alteration is located in exon 1 (coding exon 1) of the ATRIP gene. This alteration results from a C to G substitution at nucleotide position 85, causing the proline (P) at amino acid position 29 to be replaced by an alanine (A). 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	Benign	0.098
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.53	.;D
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.042
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.6	M;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.38
MutPred		0.22		Loss of glycosylation at P29 (P = 0.0076);Loss of glycosylation at P29 (P = 0.0076);
MVP		0.64
MPC		0.91
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.45
gMVP		0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs530772573; hg19: chr3-48488334;