4-73078739-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_032217.5(ANKRD17):ā€‹c.7311A>Cā€‹(p.Gln2437His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

ANKRD17
NM_032217.5 missense

Scores

4
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45
Variant links:
Genes affected
ANKRD17 (HGNC:23575): (ankyrin repeat domain 17) The protein encoded by this gene belongs to the family of ankyrin repeat-containing proteins, and contains two distinct arrays of ankyrin repeats in its amino-terminal region, one with 15 ankyrin repeats, and the other with 10 ankyrin repeats. It also contains a nuclear export signal, nuclear localization signal, and a cyclin-binding RXL motif. Localization of this protein to the nucleus has been shown experimentally, and interactions between this protein and cyclin-dependent kinase 2 have been observed. It has been suggested that this protein plays a role in both DNA replication and in both anti-viral and anti-bacterial innate immune pathways. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

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;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ANKRD17. . Gene score misZ 5.3588 (greater than the threshold 3.09). Trascript score misZ 6.9945 (greater than threshold 3.09). GenCC has associacion of gene with syndromic intellectual disability, Chopra-Amiel-Gordon syndrome.
BP4
Computational evidence support a benign effect (MetaRNN=0.31854367).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ANKRD17NM_032217.5 linkuse as main transcriptc.7311A>C p.Gln2437His missense_variant 31/34 ENST00000358602.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANKRD17ENST00000358602.9 linkuse as main transcriptc.7311A>C p.Gln2437His missense_variant 31/345 NM_032217.5 O75179-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251472
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461884
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
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 provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxNov 21, 2022In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.63
BayesDel_addAF
Uncertain
0.071
D
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.18
T;.;.
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Pathogenic
0.98
D;D;D
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.32
T;T;T
MetaSVM
Uncertain
0.27
D
MutationAssessor
Uncertain
2.0
M;.;.
MutationTaster
Benign
0.73
D;D;D
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-1.9
N;N;N
REVEL
Uncertain
0.41
Sift
Pathogenic
0.0
D;D;D
Sift4G
Benign
0.16
T;T;T
Polyphen
0.99
D;.;.
Vest4
0.56
MutPred
0.13
Loss of MoRF binding (P = 0.0924);.;.;
MVP
0.67
MPC
0.34
ClinPred
0.79
D
GERP RS
3.2
Varity_R
0.32
gMVP
0.75

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: rs763113538; hg19: chr4-73944456; API