ENST00000658083.1:n.3410T>C

Variant names:

• chr3-142449134-A-G
• rs10935463
• ENST00000658083.1:n.3410T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000658083.1(ATR):​n.3410T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 337,736 control chromosomes in the GnomAD database, including 21,344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (8985 hom., cov: 33)
  • Exomes 𝑓: 0.36 (12359 hom.)
• Consequence: ATR ENST00000658083.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.349
• Publications: 5 publications found

Genes affected

ATR (HGNC:882): (ATR serine/threonine kinase) The protein encoded by this gene is a serine/threonine kinase and DNA damage sensor, activating cell cycle checkpoint signaling upon DNA stress. The encoded protein can phosphorylate and activate several proteins involved in the inhibition of DNA replication and mitosis, and can promote DNA repair, recombination, and apoptosis. This protein is also important for fragile site stability and centrosome duplication. Defects in this gene are a cause of Seckel syndrome 1. [provided by RefSeq, Aug 2017]

ATR Gene-Disease associations (from GenCC):

• Seckel syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Illumina, G2P, Ambry Genetics
• sarcoma

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome

  Inheritance: Unknown, AD Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
• Seckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• familial prostate carcinoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000295506 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-142449134-A-G is Benign according to our data. Variant chr3-142449134-A-G is described in ClinVar as [Benign]. Clinvar id is 1270471.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATR	NM_001184.4	c.*295T>C		downstream_gene_variant		ENST00000350721.9	NP_001175.2
ATR	NM_001354579.2	c.*295T>C		downstream_gene_variant			NP_001341508.1
ATR	XM_011512924.2	c.*295T>C		downstream_gene_variant			XP_011511226.1
ATR	XM_011512925.2	c.*295T>C		downstream_gene_variant			XP_011511227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATR	ENST00000350721.9	c.*295T>C		downstream_gene_variant		1	NM_001184.4	ENSP00000343741.4

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50917 AN: 151982 Hom.: 8981 Cov.: 33

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.362

GnomAD4 exome AF: 0.357 AC: 66245 AN: 185636 Hom.: 12359 AF XY: 0.354 AC XY: 34345 AN XY: 97150

African (AFR) AF: 0.196 AC: 1167 AN: 5942

American (AMR) AF: 0.324 AC: 2426 AN: 7480

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 2911 AN: 6534

East Asian (EAS) AF: 0.321 AC: 4231 AN: 13172

South Asian (SAS) AF: 0.254 AC: 5549 AN: 21842

European-Finnish (FIN) AF: 0.366 AC: 2408 AN: 6584

Middle Eastern (MID) AF: 0.376 AC: 313 AN: 832

European-Non Finnish (NFE) AF: 0.385 AC: 43171 AN: 112178

Other (OTH) AF: 0.368 AC: 4069 AN: 11072

GnomAD4 genome AF: 0.335 AC: 50939 AN: 152100 Hom.: 8985 Cov.: 33 AF XY: 0.335 AC XY: 24912 AN XY: 74334

African (AFR) AF: 0.203 AC: 8440 AN: 41522

American (AMR) AF: 0.347 AC: 5310 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1527 AN: 3470

East Asian (EAS) AF: 0.358 AC: 1855 AN: 5176

South Asian (SAS) AF: 0.271 AC: 1310 AN: 4828

European-Finnish (FIN) AF: 0.377 AC: 3965 AN: 10528

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27110 AN: 67964

Other (OTH) AF: 0.365 AC: 770 AN: 2112

Alfa AF: 0.368 Hom.: 4126

Bravo AF: 0.330

Asia WGS AF: 0.324 AC: 1124 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 16, 2018

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	-0.85
CADD	Benign	2.4
DANN	Benign	0.73
PhyloP100		-0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10935463; hg19: chr3-142167976;