rs1231979135

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001115116.2(ANKRD53):c.527C>T(p.Thr176Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

ANKRD53
NM_001115116.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.56

Publications

0 publications found

Variant links:

Genes affected

ANKRD53 (HGNC:25691): (ankyrin repeat domain 53) Involved in mitotic metaphase plate congression; regulation of microtubule cytoskeleton organization; and regulation of mitotic cytokinesis. Located in spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD53 links:

ENSG00000258881 (HGNC:):

ENSG00000258881 links:

TEX261 (HGNC:30712): (testis expressed 261) Predicted to enable COPII receptor activity. Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport. Predicted to act upstream of or within positive regulation of apoptotic process. Predicted to be located in cytoplasm. Predicted to be integral component of membrane. Predicted to be active in COPII-coated ER to Golgi transport vesicle. Predicted to be integral component of Golgi membrane and integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

TEX261 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.867

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001115116.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD53	NM_001115116.2	MANE Select	c.527C>T	p.Thr176Ile	missense	Exon 3 of 6	NP_001108588.1	Q8N9V6-1
ANKRD53	NM_001369683.1		c.425C>T	p.Thr142Ile	missense	Exon 3 of 6	NP_001356612.1	C9JZ61
ANKRD53	NM_024933.4		c.527C>T	p.Thr176Ile	missense	Exon 3 of 7	NP_079209.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD53	ENST00000360589.4	TSL:2 MANE Select	c.527C>T	p.Thr176Ile	missense	Exon 3 of 6	ENSP00000353796.3	Q8N9V6-1
ANKRD53	ENST00000272421.10	TSL:1	c.527C>T	p.Thr176Ile	missense	Exon 3 of 7	ENSP00000272421.6	Q8N9V6-2
ENSG00000258881	ENST00000606025.5	TSL:5	c.475+9145G>A		intron	N/A	ENSP00000475641.1	U3KQ87

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41470

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68048

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

Pathogenic

0.70

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.055

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.76

M_CAP

Benign

0.081

MetaRNN

Pathogenic

0.87

MetaSVM

Uncertain

0.63

MutationAssessor

Benign

1.8

PhyloP100

1.6

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-4.7

REVEL

Uncertain

0.34

Sift

Uncertain

0.028

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.70

MutPred

0.69

Loss of disorder (P = 0.0505)

MVP

0.89

MPC

1.2

ClinPred

0.98

GERP RS

5.2

Varity_R

0.42

gMVP

0.59

Mutation Taster

=87/13

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