Genetic Variant NM_138797.4:c.302T>G (chr22-37843937-A-C) – 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_138797.4(ANKRD54):c.302T>G(p.Leu101Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ANKRD54
NM_138797.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.51

Publications

0 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: 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=0.33090705).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD54	NM_138797.4	MANE Select	c.302T>G	p.Leu101Arg	missense	Exon 1 of 8	NP_620152.1	Q6NXT1-1
ANKRD54	NM_001349853.2		c.134-3703T>G		intron	N/A	NP_001336782.1
ANKRD54	NR_036556.2		n.511T>G		non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD54	ENST00000215941.9	TSL:1 MANE Select	c.302T>G	p.Leu101Arg	missense	Exon 1 of 8	ENSP00000215941.4	Q6NXT1-1
ANKRD54	ENST00000873384.1		c.302T>G	p.Leu101Arg	missense	Exon 1 of 8	ENSP00000543443.1
ANKRD54	ENST00000411961.6	TSL:5	c.302T>G	p.Leu101Arg	missense	Exon 1 of 7	ENSP00000405782.2	D3YTC9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

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

AF:

0.00

AC:

AN:

1214360

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

594524

African (AFR)

AF:

0.00

AC:

AN:

24126

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18034

East Asian (EAS)

AF:

0.00

AC:

AN:

26652

South Asian (SAS)

AF:

0.00

AC:

AN:

54112

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28778

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3450

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

994736

Other (OTH)

AF:

0.00

AC:

AN:

49172

GnomAD4 genome

Cov.:

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

0.11

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.037

Eigen

Benign

0.19

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.86

M_CAP

Pathogenic

0.56

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.55

PhyloP100

2.5

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.7

REVEL

Benign

0.19

Sift

Uncertain

0.0040

Sift4G

Benign

0.092

Polyphen

0.57

Vest4

0.64

MutPred

0.39

Gain of methylation at L101 (P = 0.0267)

MVP

0.70

MPC

0.92

ClinPred

0.91

GERP RS

5.4

PromoterAI

-0.040

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.64

gMVP

0.55

Mutation Taster

=67/33

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