Genetic Variant ANKRD65:p.Glu396Val (chr1-1419113-T-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001145210.3(ANKRD65):c.1187A>T(p.Glu396Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000886 in 1,513,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

ANKRD65
NM_001145210.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.448

Publications

1 publications found

Variant links:

Genes affected

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

ANKRD65 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012540221).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145210.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD65	NM_001145210.3	MANE Select	c.1187A>T	p.Glu396Val	missense	Exon 4 of 4	NP_001138682.1	E5RJM6-1
ANKRD65	NM_001243535.2		c.*121A>T		3_prime_UTR	Exon 3 of 3	NP_001230464.1	E5RJM6-2
ANKRD65	NM_001375659.1		c.*121A>T		3_prime_UTR	Exon 2 of 2	NP_001362588.1	E5RJM6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD65	ENST00000537107.6	TSL:5 MANE Select	c.1187A>T	p.Glu396Val	missense	Exon 4 of 4	ENSP00000445688.1	E5RJM6-1
ANKRD65	ENST00000427211.3	TSL:1	c.*121A>T		3_prime_UTR	Exon 3 of 3	ENSP00000428419.1	E5RJM6-2
ANKRD65	ENST00000520296.5	TSL:1	c.*429A>T		3_prime_UTR	Exon 3 of 3	ENSP00000429035.1	E5RJM6-3

Frequencies

GnomAD3 genomes

AF:

0.000414

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

GnomAD2 exomes

AF:

0.000126

AC:

AN:

127442

AF XY:

0.0000449

show subpopulations

Gnomad AFR exome

AF:

0.00192

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000271

GnomAD4 exome

AF:

0.0000522

AC:

AN:

1360898

Hom.:

Cov.:

AF XY:

0.0000391

AC XY:

AN XY:

664962

show subpopulations

African (AFR)

AF:

0.00203

AC:

AN:

30980

American (AMR)

AF:

0.0000888

AC:

AN:

33784

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22844

East Asian (EAS)

AF:

0.00

AC:

AN:

35194

South Asian (SAS)

AF:

0.00

AC:

AN:

73548

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5516

European-Non Finnish (NFE)

AF:

9.47e-7

AC:

AN:

1056168

Other (OTH)

AF:

0.0000711

AC:

AN:

56298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000414

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00149

AC:

AN:

41580

American (AMR)

AF:

0.0000653

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000578

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.2

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.0021

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.23

M_CAP

Benign

0.011

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.45

PrimateAI

Benign

0.30

PROVEAN

Benign

0.41

REVEL

Benign

0.026

Sift

Uncertain

0.011

Sift4G

Uncertain

0.014

Polyphen

0.018

Vest4

0.089

MVP

0.055

ClinPred

0.0057

GERP RS

-5.0

Varity_R

0.070

gMVP

0.43

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over