13-110880092-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017664.4(ANKRD10):​c.808G>A​(p.Val270Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,461,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 0.000021 ( 0 hom. )

Consequence

ANKRD10
NM_017664.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.170
Variant links:
Genes affected
ANKRD10 (HGNC:20265): (ankyrin repeat domain 10)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04234174).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANKRD10NM_017664.4 linkc.808G>A p.Val270Ile missense_variant Exon 6 of 6 ENST00000267339.6 NP_060134.2 Q9NXR5-1A0A024RE01
ANKRD10XM_024449380.2 linkc.*5G>A 3_prime_UTR_variant Exon 6 of 6 XP_024305148.1
ANKRD10NR_104587.2 linkn.1005G>A non_coding_transcript_exon_variant Exon 7 of 7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANKRD10ENST00000267339.6 linkc.808G>A p.Val270Ile missense_variant Exon 6 of 6 2 NM_017664.4 ENSP00000267339.2 Q9NXR5-1
ANKRD10ENST00000485844.1 linkn.317G>A non_coding_transcript_exon_variant Exon 3 of 3 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000482
AC:
12
AN:
248858
Hom.:
0
AF XY:
0.0000519
AC XY:
7
AN XY:
134794
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000272
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000448
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000205
AC:
30
AN:
1461528
Hom.:
0
Cov.:
32
AF XY:
0.0000275
AC XY:
20
AN XY:
726998
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000180
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000151
ExAC
AF:
0.0000494
AC:
6

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 18, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.808G>A (p.V270I) alteration is located in exon 6 (coding exon 6) of the ANKRD10 gene. This alteration results from a G to A substitution at nucleotide position 808, causing the valine (V) at amino acid position 270 to be replaced by an isoleucine (I). 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
0.068
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
10
DANN
Benign
0.83
DEOGEN2
Benign
0.0061
T
Eigen
Benign
-0.52
Eigen_PC
Benign
-0.38
FATHMM_MKL
Benign
0.38
N
LIST_S2
Benign
0.71
T
M_CAP
Benign
0.0095
T
MetaRNN
Benign
0.042
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.18
N
REVEL
Benign
0.034
Sift
Benign
0.43
T
Sift4G
Benign
0.43
T
Polyphen
0.11
B
Vest4
0.023
MutPred
0.34
Loss of loop (P = 0.0073);
MVP
0.41
MPC
0.34
ClinPred
0.030
T
GERP RS
1.6
Varity_R
0.012
gMVP
0.15

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.

Other links and lift over

dbSNP: rs755781873; hg19: chr13-111532439; COSMIC: COSV99941018; COSMIC: COSV99941018; API