NM_001184.4:c.*72T>G

Variant names:

• chr3-142449357-A-C
• rs750327573
• NM_001184.4:c.*72T>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001184.4(ATR):​c.*72T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000719 in 1,417,200 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00075 (2 hom.)
• Consequence: ATR NM_001184.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.54
• Publications: 0 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: G2P, Ambry Genetics, Illumina
• familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome

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

  Inheritance: AD Classification: MODERATE Submitted by: 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR,AD,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001184.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATR	NM_001184.4	MANE Select	c.*72T>G		3_prime_UTR	Exon 47 of 47	NP_001175.2	Q13535-1
	ATR	NM_001354579.2		c.*72T>G		3_prime_UTR	Exon 46 of 46	NP_001341508.1	Q13535-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATR	ENST00000350721.9	TSL:1 MANE Select	c.*72T>G		3_prime_UTR	Exon 47 of 47	ENSP00000343741.4	Q13535-1
	ATR	ENST00000513291.2	TSL:1	n.6716T>G		non_coding_transcript_exon	Exon 16 of 16
	ATR	ENST00000936442.1		c.*72T>G		3_prime_UTR	Exon 46 of 46	ENSP00000606501.1

Frequencies

GnomAD3 genomes AF: 0.000460 AC: 70 AN: 152266 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

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: 0.000676

Gnomad OTH AF: 0.000955

GnomAD4 exome AF: 0.000750 AC: 949 AN: 1264934 Hom.: 2 Cov.: 18 AF XY: 0.000698 AC XY: 445 AN XY: 637640

African (AFR) AF: 0.000173 AC: 5 AN: 28926

American (AMR) AF: 0.000581 AC: 25 AN: 43056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24676

East Asian (EAS) AF: 0.00 AC: 0 AN: 38364

South Asian (SAS) AF: 0.00 AC: 0 AN: 80406

European-Finnish (FIN) AF: 0.0000192 AC: 1 AN: 52124

Middle Eastern (MID) AF: 0.000573 AC: 3 AN: 5236

European-Non Finnish (NFE) AF: 0.000951 AC: 892 AN: 938436

Other (OTH) AF: 0.000428 AC: 23 AN: 53710

GnomAD4 genome AF: 0.000460 AC: 70 AN: 152266 Hom.: 0 Cov.: 33 AF XY: 0.000497 AC XY: 37 AN XY: 74392

African (AFR) AF: 0.000241 AC: 10 AN: 41478

American (AMR) AF: 0.000785 AC: 12 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000676 AC: 46 AN: 68050

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

Alfa AF: 0.000318 Hom.: 0

Bravo AF: 0.000468

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Seckel syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	11
DANN	Benign	0.75
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs750327573; hg19: chr3-142168199; COSMIC: COSV107298513;