Genetic Variant NM_022096.6:c.112G>A (chr20-10038413-G-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_022096.6(ANKEF1):c.112G>A(p.Glu38Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000564 in 1,614,072 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 0.00028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00059 ( 0 hom. )

Consequence

ANKEF1
NM_022096.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.61

Publications

3 publications found

Variant links:

Genes affected

ANKEF1 (HGNC:15803): (ankyrin repeat and EF-hand domain containing 1) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ANKEF1 links:

SNAP25-AS1 (HGNC:44312): (SNAP25 antisense RNA 1)

SNAP25-AS1 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=0.04084176).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022096.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKEF1	NM_022096.6	MANE Select	c.112G>A	p.Glu38Lys	missense	Exon 3 of 11	NP_071379.3
ANKEF1	NM_198798.3		c.112G>A	p.Glu38Lys	missense	Exon 2 of 10	NP_942093.1	Q9NU02
ANKEF1	NM_001303472.2		c.-502G>A		5_prime_UTR	Exon 2 of 11	NP_001290401.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKEF1	ENST00000378392.6	TSL:1 MANE Select	c.112G>A	p.Glu38Lys	missense	Exon 3 of 11	ENSP00000367644.1	Q9NU02
ANKEF1	ENST00000378380.4	TSL:2	c.112G>A	p.Glu38Lys	missense	Exon 2 of 10	ENSP00000367631.3	Q9NU02
ANKEF1	ENST00000937999.1		c.112G>A	p.Glu38Lys	missense	Exon 2 of 10	ENSP00000608058.1

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000342

AC:

AN:

251412

AF XY:

0.000353

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000924

Gnomad NFE exome

AF:

0.000510

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000593

AC:

867

AN:

1461768

Hom.:

Cov.:

AF XY:

0.000602

AC XY:

438

AN XY:

727166

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33476

American (AMR)

AF:

0.0000224

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.000992

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000710

AC:

790

AN:

1111918

Other (OTH)

AF:

0.000315

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

101

151

202

252

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

108

144

180

<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:

0.000282

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

41570

American (AMR)

AF:

0.000196

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000441

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

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:

0.000515

Hom.:

Bravo

AF:

0.000227

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000296

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000415

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

0.098

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.049

MetaRNN

Benign

0.041

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.3

PhyloP100

1.6

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.4

REVEL

Benign

0.061

Sift

Benign

0.16

Sift4G

Benign

0.24

Polyphen

0.38

Vest4

0.31

MVP

0.54

MPC

0.30

ClinPred

0.021

GERP RS

2.8

Varity_R

0.052

gMVP

0.42

Mutation Taster

=95/5

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