3-142453938-T-C

Variant names:

• chr3-142453938-T-C
• rs9816736
• NM_001184.4:c.7656-705A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001184.4(ATR):​c.7656-705A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 152,078 control chromosomes in the GnomAD database, including 30,328 homozygotes. 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 0.62 (30328 hom., cov: 32)
• Consequence: ATR NM_001184.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

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.7656-705A>G		intron	N/A	NP_001175.2	Q13535-1
	ATR	NM_001354579.2		c.7464-705A>G		intron	N/A	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.7656-705A>G		intron	N/A	ENSP00000343741.4	Q13535-1
	ATR	ENST00000513291.2	TSL:1	n.2840-705A>G		intron	N/A
	ATR	ENST00000936442.1		c.7503-705A>G		intron	N/A	ENSP00000606501.1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94428 AN: 151958 Hom.: 30284 Cov.: 32

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.619

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.613

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.622 AC: 94517 AN: 152078 Hom.: 30328 Cov.: 32 AF XY: 0.614 AC XY: 45634 AN XY: 74346

African (AFR) AF: 0.787 AC: 32652 AN: 41492

American (AMR) AF: 0.526 AC: 8029 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1939 AN: 3466

East Asian (EAS) AF: 0.469 AC: 2422 AN: 5164

South Asian (SAS) AF: 0.442 AC: 2134 AN: 4826

European-Finnish (FIN) AF: 0.544 AC: 5749 AN: 10576

Middle Eastern (MID) AF: 0.606 AC: 177 AN: 292

European-Non Finnish (NFE) AF: 0.581 AC: 39478 AN: 67974

Other (OTH) AF: 0.617 AC: 1302 AN: 2110

Alfa AF: 0.600 Hom.: 5239

Bravo AF: 0.628

Asia WGS AF: 0.505 AC: 1754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.34
DANN	Benign	0.41
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

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: rs9816736; hg19: chr3-142172780;