Genetic Variant NM_022096.6:c.35A>G (chr20-10038336-A-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_022096.6(ANKEF1):c.35A>G(p.Gln12Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ANKEF1
NM_022096.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.43

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.812

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.35A>G	p.Gln12Arg	missense	Exon 3 of 11	NP_071379.3
ANKEF1	NM_198798.3		c.35A>G	p.Gln12Arg	missense	Exon 2 of 10	NP_942093.1	Q9NU02
ANKEF1	NM_001303472.2		c.-579A>G		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.35A>G	p.Gln12Arg	missense	Exon 3 of 11	ENSP00000367644.1	Q9NU02
ANKEF1	ENST00000378380.4	TSL:2	c.35A>G	p.Gln12Arg	missense	Exon 2 of 10	ENSP00000367631.3	Q9NU02
ANKEF1	ENST00000937999.1		c.35A>G	p.Gln12Arg	missense	Exon 2 of 10	ENSP00000608058.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1432428

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

707388

African (AFR)

AF:

0.00

AC:

AN:

32758

American (AMR)

AF:

0.00

AC:

AN:

43454

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25596

East Asian (EAS)

AF:

0.00

AC:

AN:

39142

South Asian (SAS)

AF:

0.00

AC:

AN:

81280

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52922

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5654

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1092594

Other (OTH)

AF:

0.00

AC:

AN:

59028

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

Pathogenic

0.74

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Uncertain

0.13

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.072

MetaRNN

Pathogenic

0.81

MetaSVM

Uncertain

-0.046

MutationAssessor

Uncertain

2.7

PhyloP100

7.4

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.52

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.74

MutPred

0.39

Gain of MoRF binding (P = 0.0123)

MVP

0.89

MPC

0.75

ClinPred

0.96

GERP RS

5.9

Varity_R

0.66

gMVP

0.77

Mutation Taster

=74/26

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over