Variant 4-124669663-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_020337.3(ANKRD50):c.3614C>T(p.Pro1205Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,612,870 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: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ANKRD50
NM_020337.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.17

Variant links:

Genes affected

ANKRD50 (HGNC:29223): (ankyrin repeat domain containing 50) Involved in endocytic recycling. Predicted to be located in endosome. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD50 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.76

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ANKRD50	NM_020337.3 linkuse as main transcript	c.3614C>T	p.Pro1205Leu	missense_variant	4/5	ENST00000504087.6
ANKRD50	NM_001167882.2 linkuse as main transcript	c.3077C>T	p.Pro1026Leu	missense_variant	3/4
ANKRD50	XM_017008471.2 linkuse as main transcript	c.3614C>T	p.Pro1205Leu	missense_variant	3/4
ANKRD50	XM_047415992.1 linkuse as main transcript	c.3614C>T	p.Pro1205Leu	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD50	ENST00000504087.6 linkuse as main transcript	c.3614C>T	p.Pro1205Leu	missense_variant	4/5	2	NM_020337.3	P1	Q9ULJ7-1
ANKRD50	ENST00000515641.1 linkuse as main transcript	c.3077C>T	p.Pro1026Leu	missense_variant	3/4	2			Q9ULJ7-2

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

AF:

6.85e-7

AC:

AN:

1460780

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726606

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.067

T;.

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.068

MetaRNN

Pathogenic

0.76

D;D

MetaSVM

Benign

-0.30

MutationAssessor

Benign

0.90

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.6

N;N

REVEL

Uncertain

0.38

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.059

T;T

Polyphen

1.0

D;.

Vest4

0.91

MutPred

0.34

Gain of helix (P = 0.027);.;

MVP

0.76

MPC

0.33

ClinPred

0.88

GERP RS

5.3

Varity_R

0.26

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over