NM_130384.3:c.34C>G

Variant names:

• chr3-48446879-C-G
• rs2039687871
• NM_130384.3:c.34C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_130384.3(ATRIP):​c.34C>G​(p.Arg12Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000801 in 1,248,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R12P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: ATRIP NM_130384.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13707909).

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.34C>G	p.Arg12Gly	missense	Exon 1 of 13	NP_569055.1	Q8WXE1-1
	ATRIP	NM_032166.4		c.34C>G	p.Arg12Gly	missense	Exon 1 of 12	NP_115542.2
	ATRIP	NM_001271022.2		c.-218+80C>G		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.34C>G	p.Arg12Gly	missense	Exon 1 of 13	ENSP00000323099.3	Q8WXE1-1
	ATRIP	ENST00000346691.9	TSL:1	c.34C>G	p.Arg12Gly	missense	Exon 1 of 12	ENSP00000302338.5	Q8WXE1-2
	ATRIP	ENST00000949799.1		c.34C>G	p.Arg12Gly	missense	Exon 1 of 14	ENSP00000619858.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.01e-7 AC: 1 AN: 1248210 Hom.: 0 Cov.: 31 AF XY: 0.00000164 AC XY: 1 AN XY: 610280

African (AFR) AF: 0.0000397 AC: 1 AN: 25172

American (AMR) AF: 0.00 AC: 0 AN: 17104

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16664

East Asian (EAS) AF: 0.00 AC: 0 AN: 30788

South Asian (SAS) AF: 0.00 AC: 0 AN: 48838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43700

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3622

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1012044

Other (OTH) AF: 0.00 AC: 0 AN: 50278

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.080
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.036
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.76	P
Vest4		0.32
MutPred		0.17		Gain of ubiquitination at K10 (P = 0.02)
MVP		0.39
MPC		0.53
ClinPred		0.89	D
GERP RS		2.4
PromoterAI		0.014	Neutral
Varity_R		0.14
gMVP		0.22
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs2039687871; hg19: chr3-48488283;