3-48446745-C-G

Variant names:

• chr3-48446745-C-G
• rs116253015
• NM_130384.3:c.-101C>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_130384.3(ATRIP):​c.-101C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 1,304,516 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (62 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (38 hom.)
• Consequence: ATRIP NM_130384.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.625

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]

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]

ENSG00000244380 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 3-48446745-C-G is Benign according to our data. Variant chr3-48446745-C-G is described in ClinVar as [Benign]. Clinvar id is 1262894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.053 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATRIP	NM_130384.3	c.-101C>G		5_prime_UTR_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	c.-101C>G		5_prime_UTR_variant	Exon 1 of 13	1	NM_130384.3	ENSP00000323099.3

Frequencies

GnomAD3 genomes AF: 0.0169 AC: 2570 AN: 152030 Hom.: 62 Cov.: 33

Gnomad AFR AF: 0.0547

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00903

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00110

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.00232 AC: 2673 AN: 1152374 Hom.: 38 Cov.: 24 AF XY: 0.00225 AC XY: 1248 AN XY: 554224

Gnomad4 AFR exome AF: 0.0571

Gnomad4 AMR exome AF: 0.00512

Gnomad4 ASJ exome AF: 0.0169

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000125

Gnomad4 FIN exome AF: 0.0000599

Gnomad4 NFE exome AF: 0.000671

Gnomad4 OTH exome AF: 0.00628

GnomAD4 genome AF: 0.0170 AC: 2586 AN: 152142 Hom.: 62 Cov.: 33 AF XY: 0.0169 AC XY: 1257 AN XY: 74368

Gnomad4 AFR AF: 0.0549

Gnomad4 AMR AF: 0.00902

Gnomad4 ASJ AF: 0.0187

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00110

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0132 Hom.: 5

Bravo AF: 0.0193

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

- -

Feb 04, 2019

GeneDx

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	-0.76
CADD	Benign	16
DANN	Benign	0.73

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: rs116253015; hg19: chr3-48488149;