Genetic Variant ANKRD54:c.*129G>A (chr22-37831814-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138797.4(ANKRD54):c.*129G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,090 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ANKRD54
NM_138797.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.71

Publications

5 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:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138797.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANKRD54	NM_138797.4	MANE Select	c.*129G>A	3_prime_UTR	Exon 8 of 8	NP_620152.1	Q6NXT1-1
ANKRD54	NM_001349853.2		c.*129G>A	3_prime_UTR	Exon 8 of 8	NP_001336782.1
ANKRD54	NM_001363839.1		c.*129G>A	3_prime_UTR	Exon 8 of 8	NP_001350768.1	B5MCX7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANKRD54	ENST00000215941.9	TSL:1 MANE Select	c.*129G>A	3_prime_UTR	Exon 8 of 8	ENSP00000215941.4	Q6NXT1-1
ANKRD54	ENST00000873384.1		c.*129G>A	3_prime_UTR	Exon 8 of 8	ENSP00000543443.1
ANKRD54	ENST00000957324.1		c.*129G>A	3_prime_UTR	Exon 7 of 7	ENSP00000627383.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

739582

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

375838

African (AFR)

AF:

0.00

AC:

AN:

18534

American (AMR)

AF:

0.00

AC:

AN:

24958

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16206

East Asian (EAS)

AF:

0.00

AC:

AN:

32316

South Asian (SAS)

AF:

0.00

AC:

AN:

55376

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32134

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4094

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

520410

Other (OTH)

AF:

0.00

AC:

AN:

35554

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41422

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2094

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:

0.00

Hom.:

248

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.9

(source)

DANN

Benign

0.63

PhyloP100

1.7

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

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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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over