Variant 2-240500538-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001282771.3(ANKMY1):c.2554G>A(p.Asp852Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000799 in 1,614,148 control chromosomes in the GnomAD database, including 3 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00084 ( 3 hom. )

Consequence

ANKMY1
NM_001282771.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.14

Variant links:

Genes affected

ANKMY1 (HGNC:20987): (ankyrin repeat and MYND domain containing 1) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ANKMY1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10395956).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKMY1	NM_001282771.3 linkuse as main transcript	c.2554G>A	p.Asp852Asn	missense_variant	14/18	ENST00000401804.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKMY1	ENST00000401804.6 linkuse as main transcript	c.2554G>A	p.Asp852Asn	missense_variant	14/18	1	NM_001282771.3	P2

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000434

AC:

109

AN:

251358

Hom.:

AF XY:

0.000420

AC XY:

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000669

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000837

AC:

1223

AN:

1461810

Hom.:

Cov.:

AF XY:

0.000806

AC XY:

586

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000487

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.00101

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.000433

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000779

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000687

Hom.:

Bravo

AF:

0.000408

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000412

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000981

EpiControl

AF:

0.00124

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

Apr 12, 2022

The c.2287G>A (p.D763N) alteration is located in exon 13 (coding exon 12) of the ANKMY1 gene. This alteration results from a G to A substitution at nucleotide position 2287, causing the aspartic acid (D) at amino acid position 763 to be replaced by an asparagine (N). 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

0.11

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.29

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.048

T;.;T;.;.;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.38

LIST_S2

Uncertain

0.91

D;D;D;D;D;D

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.10

T;T;T;T;T;T

MetaSVM

Benign

-0.58

MutationTaster

Benign

0.96

D;D;D;D;D;D;D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.1

N;N;N;N;N;N

REVEL

Benign

0.26

Sift

Benign

0.99

T;T;T;T;T;T

Sift4G

Benign

0.18

T;T;T;T;T;T

Polyphen

0.98

D;D;D;D;.;.

Vest4

0.37

MVP

0.84

ClinPred

0.048

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.48

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