Genetic Variant ANKRD65:p.Glu389Lys (chr1-1419135-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145210.3(ANKRD65):c.1165G>A(p.Glu389Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000261 in 1,530,088 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

ANKRD65
NM_001145210.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.244

Publications

19 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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05985129).

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
ANKRD65	NM_001145210.3	MANE Select	c.1165G>A	p.Glu389Lys	missense	Exon 4 of 4	NP_001138682.1
ANKRD65	NM_001243535.2		c.*99G>A		3_prime_UTR	Exon 3 of 3	NP_001230464.1
ANKRD65	NM_001375659.1		c.*99G>A		3_prime_UTR	Exon 2 of 2	NP_001362588.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ANKRD65	ENST00000537107.6	TSL:5 MANE Select	c.1165G>A	p.Glu389Lys	missense	Exon 4 of 4	ENSP00000445688.1
ANKRD65	ENST00000427211.3	TSL:1	c.*99G>A		3_prime_UTR	Exon 3 of 3	ENSP00000428419.1
ANKRD65	ENST00000520296.5	TSL:1	c.*407G>A		3_prime_UTR	Exon 3 of 3	ENSP00000429035.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

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

GnomAD4 exome

AF:

0.00000218

AC:

AN:

1377922

Hom.:

Cov.:

AF XY:

0.00000296

AC XY:

AN XY:

676008

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31226

American (AMR)

AF:

0.00

AC:

AN:

34854

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24092

East Asian (EAS)

AF:

0.0000283

AC:

AN:

35330

South Asian (SAS)

AF:

0.00

AC:

AN:

76978

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5616

European-Non Finnish (NFE)

AF:

0.00000188

AC:

AN:

1065414

Other (OTH)

AF:

0.00

AC:

AN:

56996

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.00000657

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41456

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.00021

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.31

M_CAP

Benign

0.019

MetaRNN

Benign

0.060

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.24

PrimateAI

Benign

0.39

PROVEAN

Benign

0.010

REVEL

Benign

0.065

Sift

Benign

0.47

Sift4G

Uncertain

0.037

Polyphen

0.0

Vest4

0.20

MutPred

0.35

Gain of ubiquitination at E389 (P = 0.0075)

MVP

0.085

ClinPred

0.094

GERP RS

0.25

Varity_R

0.024

gMVP

0.41

Mutation Taster

=99/1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over