NM_130384.3:c.60delC

Variant names:

• chr3-48446901-GC-G
• NM_130384.3:c.60delC

Variant summary

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

The NM_130384.3(ATRIP):​c.60delC​(p.Gly21AlafsTer51) variant causes a frameshift 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 (★). Synonymous variant affecting the same amino acid position (i.e. P20P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATRIP NM_130384.3 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.614
• Publications: 0 publications found

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:):

CCDC51 (HGNC:25714): (coiled-coil domain containing 51) Enables mitochondrial ATP-gated potassium channel activity. Involved in potassium ion transmembrane transport. Is integral component of mitochondrial inner membrane. Part of mitochondrial ATP-gated potassium channel complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130384.3. 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
	ATRIP	NM_130384.3	MANE Select	c.60delC	p.Gly21AlafsTer51	frameshift	Exon 1 of 13	NP_569055.1	Q8WXE1-1
	ATRIP	NM_032166.4		c.60delC	p.Gly21AlafsTer51	frameshift	Exon 1 of 12	NP_115542.2
	ATRIP	NM_001271022.2		c.-218+106delC		intron	N/A	NP_001257951.1	Q8WXE1-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATRIP	ENST00000320211.10	TSL:1 MANE Select	c.60delC	p.Gly21AlafsTer51	frameshift	Exon 1 of 13	ENSP00000323099.3	Q8WXE1-1
	ATRIP	ENST00000346691.9	TSL:1	c.60delC	p.Gly21AlafsTer51	frameshift	Exon 1 of 12	ENSP00000302338.5	Q8WXE1-2
	ATRIP	ENST00000949799.1		c.60delC	p.Gly21AlafsTer51	frameshift	Exon 1 of 14	ENSP00000619858.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1230466 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 599616

African (AFR) AF: 0.00 AC: 0 AN: 25002

American (AMR) AF: 0.00 AC: 0 AN: 11892

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16486

East Asian (EAS) AF: 0.00 AC: 0 AN: 29738

South Asian (SAS) AF: 0.00 AC: 0 AN: 48784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3864

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1002466

Other (OTH) AF: 0.00 AC: 0 AN: 49874

GnomAD4 genome Cov.: 32

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
PhyloP100		-0.61

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

hg19: chr3-48488305;