Genetic Variant ANKRD54:c.133+561T>A (chr22-37847668-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001349853.2(ANKRD54):c.133+561T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 479,318 control chromosomes in the GnomAD database, including 87,543 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.58 ( 26130 hom., cov: 27)

Exomes 𝑓: 0.61 ( 61413 hom. )

Consequence

ANKRD54
NM_001349853.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.19

Publications

16 publications found

Variant links:

Genes affected

ANKRD54 (HGNC:25185): (ankyrin repeat domain 54) Predicted to enable protein kinase regulator activity. Predicted to be involved in positive regulation of erythrocyte differentiation; regulation of intracellular signal transduction; and regulation of protein kinase activity. Predicted to act upstream of or within nucleocytoplasmic transport. Predicted to be located in midbody. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD54 links:

MIR659 (HGNC:32915): (microRNA 659) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR659 links:

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new If you want to explore the variant's impact on the transcript NM_001349853.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349853.2. 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
	ANKRD54	NM_001349853.2		c.133+561T>A		intron	N/A	NP_001336782.1
	MIR659	NR_030396.1		n.*10T>A		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD54	ENST00000609454.5	TSL:3	c.-28+1269T>A		intron	N/A	ENSP00000477088.1	V9GYU2
	MIR659	ENST00000384963.1	TSL:6	n.*10T>A		downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.584

AC:

88346

AN:

151296

Hom.:

26121

Cov.:

show subpopulations

Gnomad AFR

AF:

0.534

Gnomad AMI

AF:

0.538

Gnomad AMR

AF:

0.588

Gnomad ASJ

AF:

0.564

Gnomad EAS

AF:

0.861

Gnomad SAS

AF:

0.652

Gnomad FIN

AF:

0.575

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.591

Gnomad OTH

AF:

0.581

GnomAD2 exomes

AF:

0.607

AC:

121230

AN:

199814

AF XY:

0.607

show subpopulations

Gnomad AFR exome

AF:

0.529

Gnomad AMR exome

AF:

0.578

Gnomad ASJ exome

AF:

0.561

Gnomad EAS exome

AF:

0.871

Gnomad FIN exome

AF:

0.580

Gnomad NFE exome

AF:

0.586

Gnomad OTH exome

AF:

0.592

GnomAD4 exome

AF:

0.608

AC:

199206

AN:

327904

Hom.:

61413

Cov.:

AF XY:

0.612

AC XY:

115881

AN XY:

189404

show subpopulations

African (AFR)

AF:

0.522

AC:

3629

AN:

6958

American (AMR)

AF:

0.580

AC:

11560

AN:

19932

Ashkenazi Jewish (ASJ)

AF:

0.562

AC:

5409

AN:

9630

East Asian (EAS)

AF:

0.868

AC:

9507

AN:

10948

South Asian (SAS)

AF:

0.658

AC:

36028

AN:

54742

European-Finnish (FIN)

AF:

0.583

AC:

18609

AN:

31894

Middle Eastern (MID)

AF:

0.619

AC:

1691

AN:

2730

European-Non Finnish (NFE)

AF:

0.590

AC:

104070

AN:

176488

Other (OTH)

AF:

0.597

AC:

8703

AN:

14582

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

3556

7112

10669

14225

17781

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

668

1336

2004

2672

3340

<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:

0.584

AC:

88393

AN:

151414

Hom.:

26130

Cov.:

AF XY:

0.584

AC XY:

43181

AN XY:

73954

show subpopulations

African (AFR)

AF:

0.534

AC:

22011

AN:

41254

American (AMR)

AF:

0.588

AC:

8936

AN:

15198

Ashkenazi Jewish (ASJ)

AF:

0.564

AC:

1952

AN:

3462

East Asian (EAS)

AF:

0.861

AC:

4405

AN:

5118

South Asian (SAS)

AF:

0.652

AC:

3124

AN:

4788

European-Finnish (FIN)

AF:

0.575

AC:

6036

AN:

10506

Middle Eastern (MID)

AF:

0.578

AC:

170

AN:

294

European-Non Finnish (NFE)

AF:

0.591

AC:

40050

AN:

67794

Other (OTH)

AF:

0.583

AC:

1224

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1749

3498

5247

6996

8745

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

754

1508

2262

3016

3770

<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:

0.512

Hom.:

2755

Bravo

AF:

0.583

Asia WGS

AF:

0.708

AC:

2465

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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