dbSNP rs1645506091: ANKRD65:p.Gly263Asp (chr1-1419512-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.788G>A(p.Gly263Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,388,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

ANKRD65
NM_001145210.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.705

Publications

0 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=0.04468292).

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.788G>A	p.Gly263Asp	missense	Exon 4 of 4	NP_001138682.1	E5RJM6-1
ANKRD65	NM_001243535.2		c.247G>A	p.Ala83Thr	missense	Exon 3 of 3	NP_001230464.1	E5RJM6-2
ANKRD65	NM_001375659.1		c.247G>A	p.Ala83Thr	missense	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.788G>A	p.Gly263Asp	missense	Exon 4 of 4	ENSP00000445688.1	E5RJM6-1
ANKRD65	ENST00000427211.3	TSL:1	c.247G>A	p.Ala83Thr	missense	Exon 3 of 3	ENSP00000428419.1	E5RJM6-2
ANKRD65	ENST00000520296.5	TSL:1	c.*30G>A		3_prime_UTR	Exon 3 of 3	ENSP00000429035.1	E5RJM6-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000216

AC:

AN:

1388874

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

685150

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000317

AC:

AN:

31570

American (AMR)

AF:

0.00

AC:

AN:

35604

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25076

East Asian (EAS)

AF:

0.00

AC:

AN:

35678

South Asian (SAS)

AF:

0.00

AC:

AN:

79066

European-Finnish (FIN)

AF:

0.0000245

AC:

AN:

40784

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

9.28e-7

AC:

AN:

1077572

Other (OTH)

AF:

0.00

AC:

AN:

57836

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000625500), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.342

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

0.15

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.3

(source)

DANN

Benign

0.56

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.42

M_CAP

Benign

0.019

MetaRNN

Benign

0.045

MetaSVM

Benign

-0.97

PhyloP100

-0.70

PROVEAN

Benign

-0.27

REVEL

Benign

0.046

Sift

Pathogenic

0.0

Sift4G

Benign

0.28

Vest4

0.23

MutPred

0.20

Gain of relative solvent accessibility (P = 0.0098)

MVP

0.030

ClinPred

0.018

GERP RS

-8.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.040

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over