Genetic Variant ANKRD44:p.Glu959Lys (chr2-196993631-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001195144.2(ANKRD44):c.2875G>A(p.Glu959Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000786 in 1,398,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 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: 0.0000079 ( 0 hom. )

Consequence

ANKRD44
NM_001195144.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.29

Publications

0 publications found

Variant links:

Genes affected

ANKRD44 (HGNC:25259): (ankyrin repeat domain 44)

ANKRD44 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32462662).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195144.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD44	NM_001195144.2	MANE Select	c.2875G>A	p.Glu959Lys	missense	Exon 27 of 28	NP_001182073.1	Q8N8A2-1
ANKRD44	NM_001367495.1		c.2929G>A	p.Glu977Lys	missense	Exon 27 of 28	NP_001354424.1
ANKRD44	NM_001367497.1		c.2875G>A	p.Glu959Lys	missense	Exon 27 of 28	NP_001354426.1	A0A2R8Y7Y4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD44	ENST00000282272.15	TSL:5 MANE Select	c.2875G>A	p.Glu959Lys	missense	Exon 27 of 28	ENSP00000282272.9	Q8N8A2-1
ANKRD44	ENST00000424317.5	TSL:1	c.2320G>A	p.Glu774Lys	missense	Exon 21 of 22	ENSP00000403415.1	H7C209
ANKRD44	ENST00000647377.1		c.2875G>A	p.Glu959Lys	missense	Exon 27 of 28	ENSP00000496628.1	A0A2R8Y7Y4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

151146

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000786

AC:

AN:

1398766

Hom.:

Cov.:

AF XY:

0.00000435

AC XY:

AN XY:

689884

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31598

American (AMR)

AF:

0.00

AC:

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35740

South Asian (SAS)

AF:

0.00

AC:

AN:

79220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.00000927

AC:

AN:

1079072

Other (OTH)

AF:

0.0000172

AC:

AN:

58162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

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

0.21

BayesDel_addAF

Benign

0.00029

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.91

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.60

PhyloP100

4.3

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.48

REVEL

Benign

0.18

Sift

Benign

0.20

Sift4G

Benign

0.47

Vest4

0.32

MVP

0.53

ClinPred

0.65

GERP RS

5.2

Varity_R

0.14

gMVP

0.32

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