10-37132246-C-T

Variant summary

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

The NM_052997.3(ANKRD30A):​c.517C>T​(p.Leu173Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000246 in 1,585,146 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 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ANKRD30A
NM_052997.3 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.416
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1267856).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANKRD30ANM_052997.3 linkc.517C>T p.Leu173Phe missense_variant Exon 4 of 36 ENST00000361713.2 NP_443723.3 Q9BXX3R4GNA2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANKRD30AENST00000361713.2 linkc.517C>T p.Leu173Phe missense_variant Exon 4 of 36 5 NM_052997.3 ENSP00000354432.2 Q9BXX3R4GNA2
ANKRD30AENST00000374660.7 linkc.517C>T p.Leu173Phe missense_variant Exon 4 of 42 5 ENSP00000363792.2 Q5W026
ANKRD30AENST00000602533.7 linkc.517C>T p.Leu173Phe missense_variant Exon 4 of 36 5 ENSP00000473551.2 Q9BXX3

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152132
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000338
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.00
GnomAD3 exomes
AF:
0.0000260
AC:
6
AN:
231140
Hom.:
0
AF XY:
0.0000239
AC XY:
3
AN XY:
125400
show subpopulations
Gnomad AFR exome
AF:
0.000199
Gnomad AMR exome
AF:
0.0000692
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:
0.00
Gnomad OTH exome
AF:
0.000181
GnomAD4 exome
AF:
0.0000161
AC:
23
AN:
1433014
Hom.:
0
Cov.:
29
AF XY:
0.00000844
AC XY:
6
AN XY:
711152
show subpopulations
Gnomad4 AFR exome
AF:
0.000463
Gnomad4 AMR exome
AF:
0.0000505
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:
0.00
Gnomad4 OTH exome
AF:
0.0000843
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152132
Hom.:
0
Cov.:
33
AF XY:
0.0000942
AC XY:
7
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.000338
Gnomad4 AMR
AF:
0.0000655
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:
0.00
Alfa
AF:
0.000142
Hom.:
0
Bravo
AF:
0.000132
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000123
AC:
1
ExAC
AF:
0.0000166
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 31, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.349C>T (p.L117F) alteration is located in exon 4 (coding exon 4) of the ANKRD30A gene. This alteration results from a C to T substitution at nucleotide position 349, causing the leucine (L) at amino acid position 117 to be replaced by a phenylalanine (F). 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
0.23
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
6.0
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0026
T;T;.;.
Eigen
Benign
-0.62
Eigen_PC
Benign
-0.82
FATHMM_MKL
Benign
0.0043
N
LIST_S2
Benign
0.23
T;T;T;.
M_CAP
Benign
0.0025
T
MetaRNN
Benign
0.13
T;T;T;T
MetaSVM
Benign
-0.81
T
MutationAssessor
Benign
0.53
N;.;.;.
PrimateAI
Pathogenic
0.87
D
PROVEAN
Uncertain
-2.5
.;N;D;.
REVEL
Benign
0.17
Sift
Benign
0.11
.;T;T;.
Sift4G
Uncertain
0.053
T;T;T;T
Polyphen
0.99
D;.;.;.
Vest4
0.081
MVP
0.69
MPC
0.061
ClinPred
0.17
T
GERP RS
0.27
Varity_R
0.027
gMVP
0.089

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs368246170; hg19: chr10-37421174; COSMIC: COSV105284143; COSMIC: COSV105284143; API