rs3135940

Variant names:

• chr3-48466176-G-A
• rs3135940
• NM_130384.3:c.*622G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-48466176-G-A
• chr3-48466176-G-C
• chr3-48466176-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_130384.3(ATRIP):​c.*622G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000061 in 508,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000067 (0 hom.)
• Consequence: ATRIP NM_130384.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 10 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]

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]

TREX1 Gene-Disease associations (from GenCC):

• Aicardi-Goutieres syndrome 1

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• chilblain lupus 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• Aicardi-Goutieres syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial chilblain lupus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ATRIP-TREX1 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATRIP	NM_130384.3	c.*622G>A		3_prime_UTR_variant	Exon 13 of 13	ENST00000320211.10	NP_569055.1
TREX1	NM_033629.6	c.-160G>A		upstream_gene_variant		ENST00000625293.3	NP_338599.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATRIP	ENST00000320211.10	c.*622G>A		3_prime_UTR_variant	Exon 13 of 13	1	NM_130384.3	ENSP00000323099.3
TREX1	ENST00000625293.3	c.-160G>A		upstream_gene_variant		6	NM_033629.6	ENSP00000486676.2

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152234 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000955

GnomAD4 exome AF: 0.0000674 AC: 24 AN: 356156 Hom.: 0 Cov.: 0 AF XY: 0.0000373 AC XY: 7 AN XY: 187664

African (AFR) AF: 0.00 AC: 0 AN: 10436

American (AMR) AF: 0.000257 AC: 4 AN: 15572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11014

East Asian (EAS) AF: 0.000222 AC: 5 AN: 22542

South Asian (SAS) AF: 0.00 AC: 0 AN: 44448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1528

European-Non Finnish (NFE) AF: 0.0000622 AC: 13 AN: 208990

Other (OTH) AF: 0.0000982 AC: 2 AN: 20374

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152234 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74370

African (AFR) AF: 0.00 AC: 0 AN: 41474

American (AMR) AF: 0.000196 AC: 3 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.000955 AC: 2 AN: 2094

Alfa AF: 0.000131 Hom.: 0

Bravo AF: 0.0000831

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.8
DANN	Benign	0.77
PhyloP100		-1.4
PromoterAI		-0.16	Neutral

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

Other links and lift over

dbSNP: rs3135940; hg19: chr3-48507575;