Variant 1-1420362-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001145210.3(ANKRD65):c.440C>A(p.Ala147Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000287 in 1,255,628 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: 𝑓 0.00019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000072 ( 0 hom. )

Consequence

ANKRD65
NM_001145210.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.53

Variant links:

Genes affected

ANKRD65 (HGNC:42950): (ankyrin repeat domain 65)

ANKRD65 links:

ANKRD65-AS1 (HGNC:55844): (ANKRD65 antisense RNA 1)

ANKRD65-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.829

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD65	NM_001145210.3 linkuse as main transcript	c.440C>A	p.Ala147Asp	missense_variant	3/4	ENST00000537107.6
ANKRD65-AS1	XR_946814.2 linkuse as main transcript	n.197G>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD65	ENST00000537107.6 linkuse as main transcript	c.440C>A	p.Ala147Asp	missense_variant	3/4	5	NM_001145210.3	P1	E5RJM6-1
ANKRD65-AS1	ENST00000428932.1 linkuse as main transcript	n.118G>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.000188

AC:

AN:

148860

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000633

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000978

GnomAD4 exome

AF:

0.00000723

AC:

AN:

1106768

Hom.:

Cov.:

AF XY:

0.00000926

AC XY:

AN XY:

540226

show subpopulations

Gnomad4 AFR exome

AF:

0.000335

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:

0.0000239

GnomAD4 genome

AF:

0.000188

AC:

AN:

148860

Hom.:

Cov.:

AF XY:

0.000221

AC XY:

AN XY:

72524

show subpopulations

Gnomad4 AFR

AF:

0.000633

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000978

Bravo

AF:

0.000178

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

Nov 21, 2023

The c.440C>A (p.A147D) alteration is located in exon 3 (coding exon 2) of the ANKRD65 gene. This alteration results from a C to A substitution at nucleotide position 440, causing the alanine (A) at amino acid position 147 to be replaced by an aspartic acid (D). 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

0.95

BayesDel_addAF

Benign

-0.020

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.084

T;T

Eigen

Benign

0.13

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.13

LIST_S2

Uncertain

0.89

D;.

M_CAP

Pathogenic

0.76

MetaRNN

Pathogenic

0.83

D;D

MetaSVM

Uncertain

0.43

MutationAssessor

Pathogenic

4.8

H;H

MutationTaster

Benign

1.0

D;D;D;N

PrimateAI

Pathogenic

0.93

PROVEAN

Pathogenic

-4.6

D;.

REVEL

Pathogenic

0.68

Sift

Pathogenic

0.0

D;.

Sift4G

Uncertain

0.0060

D;D

Polyphen

1.0

D;D

Vest4

0.66

MutPred

0.57

Gain of catalytic residue at A147 (P = 0.011);Gain of catalytic residue at A147 (P = 0.011);

MVP

0.60

ClinPred

0.99

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.76

gMVP

0.62

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