Variant 2-67402895-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019002.4(ETAA1):c.463A>T(p.Met155Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,451,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

ETAA1
NM_019002.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.182

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.104515016).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETAA1	NM_019002.4 linkuse as main transcript	c.463A>T	p.Met155Leu	missense_variant	4/6	ENST00000272342.6	NP_061875.2	Q9NY74
ETAA1	XM_017004376.2 linkuse as main transcript	c.463A>T	p.Met155Leu	missense_variant	4/7		XP_016859865.1
ETAA1	XM_017004377.2 linkuse as main transcript	c.463A>T	p.Met155Leu	missense_variant	4/7		XP_016859866.1
ETAA1	XM_047444809.1 linkuse as main transcript	c.208A>T	p.Met70Leu	missense_variant	4/6		XP_047300765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETAA1	ENST00000272342.6 linkuse as main transcript	c.463A>T	p.Met155Leu	missense_variant	4/6	1	NM_019002.4	ENSP00000272342.5		Q9NY74

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1451902

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

722346

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:

0.00000271

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

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

Feb 27, 2023

The c.463A>T (p.M155L) alteration is located in exon 4 (coding exon 4) of the ETAA1 gene. This alteration results from a A to T substitution at nucleotide position 463, causing the methionine (M) at amino acid position 155 to be replaced by a leucine (L). 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

0.24

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

2.2

DANN

Benign

0.53

DEOGEN2

Benign

0.0056

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.0080

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.0

N;.

REVEL

Benign

0.061

Sift

Benign

0.19

T;.

Sift4G

Benign

0.21

T;.

Polyphen

0.029

B;.

Vest4

0.24

MutPred

0.18

Loss of disorder (P = 0.0891);Loss of disorder (P = 0.0891);

MVP

0.24

MPC

0.041

ClinPred

0.18

GERP RS

-11

Varity_R

0.084

gMVP

0.062

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over