rs55894265

Positions:

• chr3-142512277-T-A
• chr3-142512277-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001184.4(ATR):​c.4835A>T​(p.Asn1612Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATR NM_001184.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.85

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ATR. . Gene score misZ 4.3648 (greater than the threshold 3.09). Trascript score misZ 7.1274 (greater than threshold 3.09). GenCC has associacion of gene with sarcoma, Seckel syndrome, familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome, Seckel syndrome 1.
• BP4: Computational evidence support a benign effect (MetaRNN=0.112359434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATR	NM_001184.4	c.4835A>T	p.Asn1612Ile	missense_variant	27/47	ENST00000350721.9	NP_001175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATR	ENST00000350721.9	c.4835A>T	p.Asn1612Ile	missense_variant	27/47	1	NM_001184.4	ENSP00000343741	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	22
DANN	Benign	0.89
DEOGEN2	Benign	0.095	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.46
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	0.75	D;D
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.072
Sift	Benign	0.030	D
Sift4G	Benign	0.11	T
Polyphen		0.0060	B
Vest4		0.24
MutPred		0.28		Gain of glycosylation at S1609 (P = 0.0382);
MVP		0.29
MPC		0.78
ClinPred		0.17	T
GERP RS		3.9
Varity_R		0.082
gMVP		0.12

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-142231119;