chr4-73076278-G-C

Position:

chr4-73076278-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BS1BS2

The NM_032217.5(ANKRD17):c.7765C>G(p.Pro2589Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0013 in 1,609,220 control chromosomes in the GnomAD database, including 2 homozygotes. 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 Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00078 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 2 hom. )

Consequence

ANKRD17
NM_032217.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.42

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]

ANKRD17 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

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). The gene has 11 curated pathogenic missense variants (we use a threshold of 10). The gene has 15 curated benign missense variants. GenCC has associacion of the gene with syndromic intellectual disability, Chopra-Amiel-Gordon syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.018128008).

BP6

Variant 4-73076278-G-C is Benign according to our data. Variant chr4-73076278-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3044401.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000783 (119/151970) while in subpopulation NFE AF= 0.00138 (94/67980). AF 95% confidence interval is 0.00116. There are 0 homozygotes in gnomad4. There are 52 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 119 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD17	NM_032217.5 link	c.7765C>G	p.Pro2589Ala	missense_variant	34/34	ENST00000358602.9	NP_115593.3	O75179-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ANKRD17	ENST00000358602.9 link	c.7765C>G	p.Pro2589Ala	missense_variant	34/34	5	NM_032217.5	ENSP00000351416.4	O75179-1
ANKRD17	ENST00000509867.6 link	c.7426C>G	p.Pro2476Ala	missense_variant	34/34	1		ENSP00000427151.2	O75179-7
ANKRD17	ENST00000558247.5 link	c.7414C>G	p.Pro2472Ala	missense_variant	34/34	1		ENSP00000453434.1	H0YM23
ANKRD17	ENST00000330838.10 link	c.7012C>G	p.Pro2338Ala	missense_variant	33/33	2		ENSP00000332265.6	O75179-6

Frequencies

GnomAD3 genomes

AF:

0.000784

AC:

119

AN:

151852

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000475

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00138

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000866

AC:

214

AN:

247134

Hom.:

AF XY:

0.000920

AC XY:

123

AN XY:

133764

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.000238

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000166

Gnomad FIN exome

AF:

0.000232

Gnomad NFE exome

AF:

0.00171

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.00136

AC:

1976

AN:

1457250

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

897

AN XY:

724970

show subpopulations

Gnomad4 AFR exome

AF:

0.000151

Gnomad4 AMR exome

AF:

0.000181

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000187

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.00169

Gnomad4 OTH exome

AF:

0.000981

GnomAD4 genome

AF:

0.000783

AC:

119

AN:

151970

Hom.:

Cov.:

AF XY:

0.000700

AC XY:

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000475

Gnomad4 NFE

AF:

0.00138

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00134

Hom.:

Bravo

AF:

0.000971

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000914

AC:

111

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ANKRD17-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 28, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.11

T;.;.

Eigen

Benign

-0.081

Eigen_PC

Benign

0.15

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.0041

MetaRNN

Benign

0.018

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.34

N;.;.

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.65

N;N;N

REVEL

Benign

0.057

Sift

Benign

0.35

T;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.0080

B;.;.

Vest4

0.25

MVP

0.31

MPC

0.29

ClinPred

0.017

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.052

gMVP

0.25

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over