chr3-48466209-G-C

Position:

• chr3-48466209-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_130384.3(ATRIP):​c.*655G>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00239 in 563,800 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (4 hom.)
• Consequence: ATRIP NM_130384.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 4.24

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]

TREX1 (HGNC:12269): (three prime repair exonuclease 1) This gene encodes a nuclear protein with 3' exonuclease activity. The encoded protein may play a role in DNA repair and serve as a proofreading function for DNA polymerase. Mutations in this gene result in Aicardi-Goutieres syndrome, chilblain lupus, Cree encephalitis, and other diseases of the immune system. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2012]

ATRIP-TREX1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATRIP	NM_130384.3	c.*655G>C		3_prime_UTR_variant	13/13	ENST00000320211.10	NP_569055.1
ATRIP-TREX1	NR_153405.1	n.3183G>C		non_coding_transcript_exon_variant	14/15
TREX1	NM_033629.6			upstream_gene_variant		ENST00000625293.3	NP_338599.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATRIP	ENST00000320211.10	c.*655G>C		3_prime_UTR_variant	13/13	1	NM_130384.3	ENSP00000323099	P1
TREX1	ENST00000625293.3			upstream_gene_variant			NM_033629.6	ENSP00000486676	P1

Frequencies

GnomAD3 genomes AF: 0.00211 AC: 321 AN: 152204 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00807

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00319

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.00250 AC: 1028 AN: 411478 Hom.: 4 Cov.: 4 AF XY: 0.00233 AC XY: 505 AN XY: 216826

Gnomad4 AFR exome AF: 0.000594

Gnomad4 AMR exome AF: 0.000768

Gnomad4 ASJ exome AF: 0.00760

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00464

Gnomad4 NFE exome AF: 0.00303

Gnomad4 OTH exome AF: 0.00216

GnomAD4 genome AF: 0.00211 AC: 321 AN: 152322 Hom.: 1 Cov.: 33 AF XY: 0.00217 AC XY: 162 AN XY: 74490

Gnomad4 AFR AF: 0.000601

Gnomad4 AMR AF: 0.000914

Gnomad4 ASJ AF: 0.00807

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00320

Gnomad4 NFE AF: 0.00319

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000319 Hom.: 0

Bravo AF: 0.00184

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

Aicardi Goutieres syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	19
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs577465983; hg19: chr3-48507608;