Genetic Variant NM_138797.4:c.350C>T (chr22-37840213-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138797.4(ANKRD54):c.350C>T(p.Ser117Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,461,700 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

ANKRD54
NM_138797.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.09

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.350C>T	p.Ser117Leu	missense	Exon 2 of 8	NP_620152.1	Q6NXT1-1
ANKRD54	NM_001363839.1		c.-6C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	NP_001350768.1	B5MCX7
ANKRD54	NM_001349853.2		c.155C>T	p.Ser52Leu	missense	Exon 2 of 8	NP_001336782.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD54	ENST00000215941.9	TSL:1 MANE Select	c.350C>T	p.Ser117Leu	missense	Exon 2 of 8	ENSP00000215941.4	Q6NXT1-1
ANKRD54	ENST00000406423.5	TSL:3	c.-6C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	ENSP00000384392.1	B5MCX7
ANKRD54	ENST00000609454.5	TSL:3	c.-6C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000477088.1	V9GYU2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251452

AF XY:

0.0000221

show subpopulations

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461700

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727160

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000243

AC:

AN:

1111904

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

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

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Uncertain

0.54

BayesDel_addAF

Benign

-0.0027

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.043

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.19

MetaRNN

Uncertain

0.48

MetaSVM

Benign

-0.50

MutationAssessor

Benign

1.3

PhyloP100

6.1

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.35

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.034

Polyphen

0.90

Vest4

0.71

MutPred

0.58

Loss of phosphorylation at S117 (P = 0.0716)

MVP

0.75

MPC

0.87

ClinPred

0.83

GERP RS

4.4

Varity_R

0.23

gMVP

0.74

Mutation Taster

=51/49

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over