3-48466219-C-T

Position:

• chr3-48466219-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_130384.3(ATRIP):​c.*665C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 576,066 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (2 hom.)
• Consequence: ATRIP NM_130384.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.179

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 3-48466219-C-T is Benign according to our data. Variant chr3-48466219-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 345767.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATRIP	NM_130384.3	c.*665C>T		3_prime_UTR_variant	13/13	ENST00000320211.10	NP_569055.1
ATRIP-TREX1	NR_153405.1	n.3193C>T		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.*665C>T		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: 0.00112 AC: 171 AN: 152150 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00289

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00194

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.00149 AC: 632 AN: 423798 Hom.: 2 Cov.: 4 AF XY: 0.00145 AC XY: 324 AN XY: 223242

Gnomad4 AFR exome AF: 0.000165

Gnomad4 AMR exome AF: 0.000424

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000350

Gnomad4 SAS exome AF: 0.00205

Gnomad4 FIN exome AF: 0.000784

Gnomad4 NFE exome AF: 0.00180

Gnomad4 OTH exome AF: 0.00209

GnomAD4 genome AF: 0.00112 AC: 170 AN: 152268 Hom.: 0 Cov.: 33 AF XY: 0.000887 AC XY: 66 AN XY: 74450

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.000847

Gnomad4 NFE AF: 0.00194

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000159 Hom.: 0

Bravo AF: 0.00119

Asia WGS AF: 0.00289 AC: 10 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Aicardi Goutieres syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations Benign:1

Likely benign, 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	-0.86
CADD	Benign	7.5
DANN	Benign	0.80
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: rs548710061; hg19: chr3-48507618;