Genetic Variant ANKAR:p.Pro10Arg (chr2-189676519-C-G) – 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_001378068.1(ANKAR):c.29C>G(p.Pro10Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000766 in 1,566,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

ANKAR
NM_001378068.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.02

Publications

0 publications found

Variant links:

Genes affected

ANKAR (HGNC:26350): (ankyrin and armadillo repeat containing) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ANKAR 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=0.014129043).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378068.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKAR	NM_001378068.1	MANE Select	c.29C>G	p.Pro10Arg	missense	Exon 2 of 23	NP_001364997.1	Q7Z5J8-1
	ANKAR	NM_144708.3		c.29C>G	p.Pro10Arg	missense	Exon 2 of 23	NP_653309.3	Q7Z5J8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKAR	ENST00000684021.1	MANE Select	c.29C>G	p.Pro10Arg	missense	Exon 2 of 23	ENSP00000507233.1	Q7Z5J8-1
ANKAR	ENST00000313581.4	TSL:1	c.29C>G	p.Pro10Arg	missense	Exon 1 of 22	ENSP00000313513.4	Q7Z5J8-1
ANKAR	ENST00000520309.5	TSL:5	c.29C>G	p.Pro10Arg	missense	Exon 2 of 23	ENSP00000427882.1	Q7Z5J8-1

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151838

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:

0.000578

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:

0.0000597

AC:

AN:

184222

AF XY:

0.0000500

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000790

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000636

AC:

AN:

1414886

Hom.:

Cov.:

AF XY:

0.00000856

AC XY:

AN XY:

701112

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32682

American (AMR)

AF:

0.00

AC:

AN:

38168

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25516

East Asian (EAS)

AF:

0.000235

AC:

AN:

38250

South Asian (SAS)

AF:

0.00

AC:

AN:

83098

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39886

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1092486

Other (OTH)

AF:

0.00

AC:

AN:

59066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

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:

0.0000198

AC:

AN:

151838

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74116

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41314

American (AMR)

AF:

0.00

AC:

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000578

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67970

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000169

AC:

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

0.12

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.58

CADD

Benign

9.3

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.0069

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.59

M_CAP

Benign

0.0048

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

-1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.4

REVEL

Benign

0.027

Sift

Benign

0.069

Sift4G

Benign

0.061

Polyphen

0.0050

Vest4

0.26

MutPred

0.30

Gain of MoRF binding (P = 0.0036)

MVP

0.41

MPC

0.13

ClinPred

0.018

GERP RS

-2.5

PromoterAI

0.077

Neutral

(source)

Varity_R

0.047

gMVP

0.41

Mutation Taster

=96/4

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over