Variant 5-56111327-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024669.3(ANKRD55):c.1421G>T(p.Arg474Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ANKRD55
NM_024669.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.59

Variant links:

Genes affected

ANKRD55 (HGNC:25681): (ankyrin repeat domain 55)

ANKRD55 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18268451).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD55	NM_024669.3 linkuse as main transcript	c.1421G>T	p.Arg474Leu	missense_variant	10/12	ENST00000341048.9
ANKRD55	XM_047417710.1 linkuse as main transcript	c.935G>T	p.Arg312Leu	missense_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD55	ENST00000341048.9 linkuse as main transcript	c.1421G>T	p.Arg474Leu	missense_variant	10/12	2	NM_024669.3	P1	Q3KP44-1
ANKRD55	ENST00000434982.2 linkuse as main transcript	c.557G>T	p.Arg186Leu	missense_variant	2/4	1			Q3KP44-2
	ENST00000645512.1 linkuse as main transcript	n.646C>A		non_coding_transcript_exon_variant	4/4
ANKRD55	ENST00000504958.6 linkuse as main transcript	c.1292G>T	p.Arg431Leu	missense_variant	8/10	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250864

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135562

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2023

The c.1421G>T (p.R474L) alteration is located in exon 10 (coding exon 9) of the ANKRD55 gene. This alteration results from a G to T substitution at nucleotide position 1421, causing the arginine (R) at amino acid position 474 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

T;T;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.79

T;T;T

M_CAP

Benign

0.043

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.;.

MutationTaster

Benign

0.94

N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.4

N;N;D

REVEL

Benign

0.19

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Vest4

0.47

MVP

0.49

MPC

0.43

ClinPred

0.72

GERP RS

3.8

Varity_R

0.15

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over