Variant 10-37129952-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_052997.3(ANKRD30A):c.281A>G(p.Asp94Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000665 in 1,580,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000069 ( 0 hom. )

Consequence

ANKRD30A
NM_052997.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.85

Variant links:

Genes affected

ANKRD30A (HGNC:17234): (ankyrin repeat domain 30A) This gene encodes a DNA-binding transcription factor that is uniquely expressed in mammary epithelium and the testis. Altered expression levels have been associated with breast cancer progression. [provided by RefSeq, Nov 2016]

ANKRD30A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30786407).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD30A	NM_052997.3 linkuse as main transcript	c.281A>G	p.Asp94Gly	missense_variant	2/36	ENST00000361713.2	NP_443723.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ANKRD30A	ENST00000361713.2 linkuse as main transcript	c.281A>G	p.Asp94Gly	missense_variant	2/36	5	NM_052997.3	ENSP00000354432	A2
ANKRD30A	ENST00000374660.7 linkuse as main transcript	c.281A>G	p.Asp94Gly	missense_variant	2/42	5		ENSP00000363792	P4
ANKRD30A	ENST00000602533.7 linkuse as main transcript	c.281A>G	p.Asp94Gly	missense_variant	2/36	5		ENSP00000473551	A2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000552

AC:

AN:

235550

Hom.:

AF XY:

0.0000389

AC XY:

AN XY:

128458

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:

0.000121

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000693

AC:

AN:

1427948

Hom.:

Cov.:

AF XY:

0.0000648

AC XY:

AN XY:

710130

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000235

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:

0.0000869

Gnomad4 OTH exome

AF:

0.0000511

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000882

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000662

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

Mar 28, 2023

The c.113A>G (p.D38G) alteration is located in exon 2 (coding exon 2) of the ANKRD30A gene. This alteration results from a A to G substitution at nucleotide position 113, causing the aspartic acid (D) at amino acid position 38 to be replaced by a glycine (G). 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

0.22

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

T;T;.;.

Eigen

Benign

-0.068

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.66

T;T;T;.

M_CAP

Benign

0.010

MetaRNN

Benign

0.31

T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.1

L;.;.;.

MutationTaster

Benign

0.98

N;N

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-4.0

.;D;D;.

REVEL

Benign

0.14

Sift

Uncertain

0.019

.;D;D;.

Sift4G

Uncertain

0.0050

D;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.36

MutPred

0.51

Loss of catalytic residue at D94 (P = 0.0741);.;.;.;

MVP

0.81

MPC

0.051

ClinPred

0.61

GERP RS

2.0

Varity_R

0.043

gMVP

0.34

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