Genetic Variant ETAA1:p.Ser39Pro (chr2-67397563-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_019002.4(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. 15/22 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
NM_019002.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.133

Publications

0 publications found

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:52635): (long intergenic non-protein coding RNA 1829)

LINC01829 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019002.4. 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
	ETAA1	NM_019002.4	MANE Select	c.115T>C	p.Ser39Pro	missense	Exon 1 of 6	NP_061875.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ETAA1	ENST00000272342.6	TSL:1 MANE Select	c.115T>C	p.Ser39Pro	missense	Exon 1 of 6	ENSP00000272342.5	Q9NY74
ETAA1	ENST00000925952.1		c.115T>C	p.Ser39Pro	missense	Exon 1 of 6	ENSP00000596011.1
ETAA1	ENST00000925951.1		c.115T>C	p.Ser39Pro	missense	Exon 1 of 6	ENSP00000596010.1

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

GnomAD2 exomes

AF:

0.000105

AC:

AN:

171570

AF XY:

0.0000974

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 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

African (AFR)

AF:

0.00

AC:

AN:

32322

American (AMR)

AF:

0.00

AC:

AN:

38502

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25392

East Asian (EAS)

AF:

0.00

AC:

AN:

37250

South Asian (SAS)

AF:

0.00

AC:

AN:

81026

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49190

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5196

European-Non Finnish (NFE)

AF:

0.000392

AC:

427

AN:

1089442

Other (OTH)

AF:

0.000358

AC:

AN:

58600

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

114

143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000151

AC:

AN:

151938

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74188

show subpopulations

African (AFR)

AF:

0.0000484

AC:

AN:

41360

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

67972

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0029

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.42

M_CAP

Benign

0.0063

MetaRNN

Benign

0.055

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.83

PhyloP100

0.13

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.2

REVEL

Benign

0.020

Sift

Benign

0.098

Sift4G

Benign

0.17

Polyphen

0.018

Vest4

0.11

MVP

0.082

MPC

0.059

ClinPred

0.057

GERP RS

-0.91

PromoterAI

-0.084

Neutral

(source)

Varity_R

0.16

gMVP

0.040

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over