10-37132255-C-G

Variant summary

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

The NM_052997.3(ANKRD30A):ā€‹c.526C>Gā€‹(p.Leu176Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000232 in 1,594,250 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000046 ( 0 hom., cov: 33)
Exomes š‘“: 0.000021 ( 0 hom. )

Consequence

ANKRD30A
NM_052997.3 missense

Scores

2
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.396
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]

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
ANKRD30ANM_052997.3 linkuse as main transcriptc.526C>G p.Leu176Val missense_variant 4/36 ENST00000361713.2 NP_443723.3 Q9BXX3R4GNA2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ANKRD30AENST00000361713.2 linkuse as main transcriptc.526C>G p.Leu176Val missense_variant 4/365 NM_052997.3 ENSP00000354432.2 Q9BXX3R4GNA2
ANKRD30AENST00000374660.7 linkuse as main transcriptc.526C>G p.Leu176Val missense_variant 4/425 ENSP00000363792.2 Q5W026
ANKRD30AENST00000602533.7 linkuse as main transcriptc.526C>G p.Leu176Val missense_variant 4/365 ENSP00000473551.2 Q9BXX3

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152192
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
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:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000213
AC:
5
AN:
234914
Hom.:
0
AF XY:
0.0000236
AC XY:
3
AN XY:
127296
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000995
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:
0.0000183
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000208
AC:
30
AN:
1442058
Hom.:
0
Cov.:
29
AF XY:
0.0000182
AC XY:
13
AN XY:
716196
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000146
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:
0.0000199
Gnomad4 OTH exome
AF:
0.0000335
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152192
Hom.:
0
Cov.:
33
AF XY:
0.0000807
AC XY:
6
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000478
Bravo
AF:
0.0000264
ExAC
AF:
0.00000828
AC:
1

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 submitterclinical testingAmbry GeneticsDec 20, 2023The c.358C>G (p.L120V) alteration is located in exon 4 (coding exon 4) of the ANKRD30A gene. This alteration results from a C to G substitution at nucleotide position 358, causing the leucine (L) at amino acid position 120 to be replaced by a valine (V). 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
Uncertain
0.39
BayesDel_addAF
Uncertain
0.077
D
BayesDel_noAF
Benign
-0.13
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.020
T;T;.;.
Eigen
Benign
-0.0097
Eigen_PC
Benign
-0.28
FATHMM_MKL
Benign
0.27
N
LIST_S2
Benign
0.42
T;T;T;.
M_CAP
Benign
0.0020
T
MetaRNN
Uncertain
0.47
T;T;T;T
MetaSVM
Uncertain
-0.078
T
MutationAssessor
Pathogenic
4.3
H;.;.;.
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-2.3
.;N;N;.
REVEL
Uncertain
0.39
Sift
Uncertain
0.0010
.;D;D;.
Sift4G
Uncertain
0.012
D;D;D;D
Polyphen
0.98
D;.;.;.
Vest4
0.46
MutPred
0.65
Loss of stability (P = 0.2917);.;.;.;
MVP
0.78
MPC
0.052
ClinPred
0.37
T
GERP RS
0.30
Varity_R
0.027
gMVP
0.40

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs751991070; hg19: chr10-37421183; API