Variant 2-67397563-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000272342.6(ETAA1):c.115T>C(p.Ser39Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0003 in 1,568,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

ETAA1
ENST00000272342.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.133

Variant links:

Genes affected

ETAA1 (HGNC:24648): (ETAA1 activator of ATR kinase) Enables protein serine/threonine kinase activator activity. Involved in several processes, including positive regulation of protein serine/threonine kinase activity; regulation of DNA damage checkpoint; and replication fork processing. Located in cytosol; nuclear replication fork; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ETAA1 links:

LINC01829 (HGNC:):

LINC01829 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.054569006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETAA1	NM_019002.4 linkuse as main transcript	c.115T>C	p.Ser39Pro	missense_variant	1/6	ENST00000272342.6	NP_061875.2	Q9NY74
ETAA1	XM_017004376.2 linkuse as main transcript	c.115T>C	p.Ser39Pro	missense_variant	1/7		XP_016859865.1
ETAA1	XM_017004377.2 linkuse as main transcript	c.115T>C	p.Ser39Pro	missense_variant	1/7		XP_016859866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETAA1	ENST00000272342.6 linkuse as main transcript	c.115T>C	p.Ser39Pro	missense_variant	1/6	1	NM_019002.4	ENSP00000272342.5		Q9NY74

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

151938

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000309

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000105

AC:

AN:

171570

Hom.:

AF XY:

0.0000974

AC XY:

AN XY:

92420

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000316

AC:

448

AN:

1416920

Hom.:

Cov.:

AF XY:

0.000304

AC XY:

213

AN XY:

700564

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000392

Gnomad4 OTH exome

AF:

0.000358

GnomAD4 genome

AF:

0.000151

AC:

AN:

151938

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74188

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000280

Hom.:

Bravo

AF:

0.000230

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000463

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.000229

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 19, 2022

The c.115T>C (p.S39P) alteration is located in exon 1 (coding exon 1) of the ETAA1 gene. This alteration results from a T to C substitution at nucleotide position 115, causing the serine (S) at amino acid position 39 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0029

T;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.42

T;T

M_CAP

Benign

0.0063

MetaRNN

Benign

0.055

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.83

L;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.2

N;.

REVEL

Benign

0.020

Sift

Benign

0.098

T;.

Sift4G

Benign

0.17

T;.

Polyphen

0.018

B;.

Vest4

0.11

MVP

0.082

MPC

0.059

ClinPred

0.057

GERP RS

-0.91

Varity_R

0.16

gMVP

0.040

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over