Genetic Variant ANKRD44:p.Ala988Thr (chr2-196989611-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001195144.2(ANKRD44):c.2962G>A(p.Ala988Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000903 in 1,549,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000092 ( 0 hom. )

Consequence

ANKRD44
NM_001195144.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.08

Publications

0 publications found

Variant links:

Genes affected

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

ANKRD44 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10688481).

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.2962G>A	p.Ala988Thr	missense	Exon 28 of 28	NP_001182073.1	Q8N8A2-1
ANKRD44	NM_001367495.1		c.*1069G>A		3_prime_UTR	Exon 28 of 28	NP_001354424.1
ANKRD44	NM_001367497.1		c.*1069G>A		3_prime_UTR	Exon 28 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.2962G>A	p.Ala988Thr	missense	Exon 28 of 28	ENSP00000282272.9	Q8N8A2-1
ANKRD44	ENST00000424317.5	TSL:1	c.2368+3972G>A		intron	N/A	ENSP00000403415.1	H7C209
ANKRD44	ENST00000871701.1		c.3016G>A	p.Ala1006Thr	missense	Exon 28 of 28	ENSP00000541760.1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000101

AC:

AN:

149132

AF XY:

0.000124

show subpopulations

Gnomad AFR exome

AF:

0.000148

Gnomad AMR exome

AF:

0.0000814

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000909

Gnomad OTH exome

AF:

0.000232

GnomAD4 exome

AF:

0.0000916

AC:

128

AN:

1397808

Hom.:

Cov.:

AF XY:

0.0000957

AC XY:

AN XY:

689448

show subpopulations

African (AFR)

AF:

0.0000633

AC:

AN:

31590

American (AMR)

AF:

0.0000280

AC:

AN:

35686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25164

East Asian (EAS)

AF:

0.00

AC:

AN:

35698

South Asian (SAS)

AF:

0.000240

AC:

AN:

79228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48116

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.0000964

AC:

104

AN:

1078668

Other (OTH)

AF:

0.0000345

AC:

AN:

57964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

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:

0.0000789

AC:

AN:

152062

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41402

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000564

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.000156

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

0.075

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.028

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.78

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.89

MutationAssessor

Benign

-0.14

PhyloP100

5.1

PrimateAI

Benign

0.38

REVEL

Benign

0.10

Sift4G

Benign

0.38

Vest4

0.10

MVP

0.47

ClinPred

0.066

GERP RS

6.1

Varity_R

0.11

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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