Variant 10-37129908-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_052997.3(ANKRD30A):c.237G>T(p.Trp79Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,555,494 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

ANKRD30A
NM_052997.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.110

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD30A	NM_052997.3 linkuse as main transcript	c.237G>T	p.Trp79Cys	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.237G>T	p.Trp79Cys	missense_variant	2/36	5	NM_052997.3	ENSP00000354432	A2
ANKRD30A	ENST00000374660.7 linkuse as main transcript	c.237G>T	p.Trp79Cys	missense_variant	2/42	5		ENSP00000363792	P4
ANKRD30A	ENST00000602533.7 linkuse as main transcript	c.237G>T	p.Trp79Cys	missense_variant	2/36	5		ENSP00000473551	A2

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000428

AC:

AN:

1403360

Hom.:

Cov.:

AF XY:

0.00000287

AC XY:

AN XY:

697532

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000491

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:

9.26e-7

Gnomad4 OTH exome

AF:

0.0000522

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000982

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 01, 2024

The c.69G>T (p.W23C) alteration is located in exon 2 (coding exon 2) of the ANKRD30A gene. This alteration results from a G to T substitution at nucleotide position 69, causing the tryptophan (W) at amino acid position 23 to be replaced by a cysteine (C). 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

Pathogenic

0.88

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0030

T;T;.;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.16

LIST_S2

Uncertain

0.95

D;D;D;.

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.44

T;T;T;T

MetaSVM

Benign

-0.47

MutationAssessor

Benign

1.3

L;.;.;.

MutationTaster

Benign

0.91

D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-2.3

.;N;N;.

REVEL

Uncertain

0.32

Sift

Uncertain

0.0030

.;D;D;.

Sift4G

Uncertain

0.028

D;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.48

MutPred

0.66

Loss of MoRF binding (P = 0.0447);.;.;.;

MVP

0.78

MPC

0.018

ClinPred

0.36

GERP RS

-0.73

Varity_R

0.090

gMVP

0.46

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