Variant 7-118236108-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_019644.4(ANKRD7):c.536A>T(p.Glu179Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,530 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ANKRD7
NM_019644.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31

Variant links:

Genes affected

ANKRD7 (HGNC:18588): (ankyrin repeat domain 7) Predicted to act upstream of or within blastocyst hatching. Located in centrosome and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD7 links:

ANKRD7 (HGNC:):

ANKRD7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28518468).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD7	NM_019644.4 linkuse as main transcript	c.536A>T	p.Glu179Val	missense_variant	4/7	ENST00000265224.9	NP_062618.2	Q92527-1A0A140VJE5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ANKRD7	ENST00000265224.9 linkuse as main transcript	c.536A>T	p.Glu179Val	missense_variant	4/7	1	NM_019644.4	ENSP00000265224.4	Q92527-1
ANKRD7	ENST00000417525.5 linkuse as main transcript	c.536A>T	p.Glu179Val	missense_variant	4/7	5		ENSP00000395595.2	C9JIJ7
ANKRD7	ENST00000477532.5 linkuse as main transcript	c.20A>T	p.Glu7Val	missense_variant	4/6	5		ENSP00000489121.1	A0A0U1RQQ7
ANKRD7	ENST00000433239.6 linkuse as main transcript	n.493A>T		non_coding_transcript_exon_variant	4/16	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248568

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134936

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:

0.00

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456530

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724902

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 09, 2024

The c.536A>T (p.E179V) alteration is located in exon 4 (coding exon 4) of the ANKRD7 gene. This alteration results from a A to T substitution at nucleotide position 536, causing the glutamic acid (E) at amino acid position 179 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

Benign

0.34

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.091

T;T;.

Eigen

Benign

-0.065

Eigen_PC

Benign

-0.079

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.85

D;D;D

M_CAP

Benign

0.076

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.6

.;M;.

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.9

.;D;.

REVEL

Benign

0.23

Sift

Uncertain

0.0010

.;D;.

Sift4G

Uncertain

0.050

T;D;D

Polyphen

0.74

.;P;.

Vest4

0.21

MutPred

0.48

.;Gain of methylation at K180 (P = 0.0412);Gain of methylation at K180 (P = 0.0412);

MVP

0.92

MPC

0.37

ClinPred

0.92

GERP RS

2.9

Varity_R

0.31

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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