Variant 2-67397542-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_019002.4(ETAA1):c.94C>G(p.Pro32Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,430,054 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: not found (cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

ETAA1
NM_019002.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.413

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:

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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=0.034555763).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETAA1	NM_019002.4 linkuse as main transcript	c.94C>G	p.Pro32Ala	missense_variant	1/6	ENST00000272342.6	NP_061875.2	Q9NY74
ETAA1	XM_017004376.2 linkuse as main transcript	c.94C>G	p.Pro32Ala	missense_variant	1/7		XP_016859865.1
ETAA1	XM_017004377.2 linkuse as main transcript	c.94C>G	p.Pro32Ala	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.94C>G	p.Pro32Ala	missense_variant	1/6	1	NM_019002.4	ENSP00000272342.5		Q9NY74

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000315

AC:

AN:

190190

Hom.:

AF XY:

0.0000389

AC XY:

AN XY:

102944

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000694

Gnomad SAS exome

AF:

0.000195

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000168

AC:

AN:

1430054

Hom.:

Cov.:

AF XY:

0.0000184

AC XY:

AN XY:

708392

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000263

Gnomad4 SAS exome

AF:

0.000231

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.12e-7

Gnomad4 OTH exome

AF:

0.0000508

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000667

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

Apr 08, 2024

The c.94C>G (p.P32A) alteration is located in exon 1 (coding exon 1) of the ETAA1 gene. This alteration results from a C to G substitution at nucleotide position 94, causing the proline (P) at amino acid position 32 to be replaced by an alanine (A). 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

0.078

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.0037

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.035

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.8

L;.

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.6

D;.

REVEL

Benign

0.038

Sift

Benign

0.13

T;.

Sift4G

Benign

1.0

T;.

Polyphen

0.030

B;.

Vest4

0.18

MutPred

0.13

Loss of loop (P = 0.0512);Loss of loop (P = 0.0512);

MVP

0.10

MPC

0.081

ClinPred

0.024

GERP RS

-2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.029

gMVP

0.024

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