18-23629914-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_173505.4(ANKRD29):​c.467G>T​(p.Gly156Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ANKRD29
NM_173505.4 missense

Scores

8
8
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.22
Variant links:
Genes affected
ANKRD29 (HGNC:27110): (ankyrin repeat domain 29) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.954

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANKRD29NM_173505.4 linkc.467G>T p.Gly156Val missense_variant Exon 6 of 10 ENST00000592179.6 NP_775776.2 Q8N6D5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANKRD29ENST00000592179.6 linkc.467G>T p.Gly156Val missense_variant Exon 6 of 10 1 NM_173505.4 ENSP00000468354.1 Q8N6D5-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461818
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000936
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 01, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.467G>T (p.G156V) alteration is located in exon 6 (coding exon 6) of the ANKRD29 gene. This alteration results from a G to T substitution at nucleotide position 467, causing the glycine (G) at amino acid position 156 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
Pathogenic
0.97
BayesDel_addAF
Pathogenic
0.40
D
BayesDel_noAF
Pathogenic
0.34
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
T;.;T
Eigen
Pathogenic
0.82
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Benign
0.62
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Uncertain
0.10
D
MetaRNN
Pathogenic
0.95
D;D;D
MetaSVM
Uncertain
0.036
D
MutationAssessor
Pathogenic
4.0
H;H;.
PrimateAI
Uncertain
0.65
T
PROVEAN
Pathogenic
-8.6
.;D;.
REVEL
Uncertain
0.64
Sift
Uncertain
0.0010
.;D;.
Sift4G
Uncertain
0.0030
D;D;.
Polyphen
0.98
D;D;.
Vest4
0.94
MutPred
0.85
Gain of MoRF binding (P = 0.3665);Gain of MoRF binding (P = 0.3665);.;
MVP
0.92
MPC
0.89
ClinPred
1.0
D
GERP RS
5.3
Varity_R
0.90
gMVP
0.79

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: rs765493407; hg19: chr18-21209878; API