Variant 7-39566480-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_020192.5(YAE1):c.62A>T(p.Asp21Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,461,866 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: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

YAE1
NM_020192.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.43

Variant links:

Genes affected

YAE1 (HGNC:24857): (YAE1 maturation factor of ABCE1) Involved in protein maturation by [4Fe-4S] cluster transfer. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

YAE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.947

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YAE1	NM_020192.5 linkuse as main transcript	c.62A>T	p.Asp21Val	missense_variant	1/3	ENST00000223273.7
YAE1	NM_001282446.2 linkuse as main transcript	c.62A>T	p.Asp21Val	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YAE1	ENST00000223273.7 linkuse as main transcript	c.62A>T	p.Asp21Val	missense_variant	1/3	1	NM_020192.5	P1	Q9NRH1-1
YAE1	ENST00000432096.2 linkuse as main transcript	c.62A>T	p.Asp21Val	missense_variant	1/3	2			Q9NRH1-2
YAE1	ENST00000448268.5 linkuse as main transcript	c.62A>T	p.Asp21Val	missense_variant	1/3	2
YAE1	ENST00000474392.1 linkuse as main transcript	n.96A>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251422

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135900

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727240

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:

0.0000144

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Aug 01, 2022

The c.62A>T (p.D21V) alteration is located in exon 1 (coding exon 1) of the YAE1D1 gene. This alteration results from a A to T substitution at nucleotide position 62, causing the aspartic acid (D) at amino acid position 21 to be replaced by a valine (V). 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

Pathogenic

0.70

BayesDel_addAF

Uncertain

0.054

BayesDel_noAF

Benign

-0.10

Cadd

Pathogenic

Dann

Uncertain

0.99

DEOGEN2

Benign

0.14

T;.;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Uncertain

0.088

MetaRNN

Pathogenic

0.95

D;D;D

MetaSVM

Uncertain

-0.24

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-7.0

D;D;D

REVEL

Uncertain

0.53

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.90

MutPred

0.82

Loss of disorder (P = 0.0267);Loss of disorder (P = 0.0267);Loss of disorder (P = 0.0267);

MVP

0.58

MPC

0.74

ClinPred

0.99

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.89

gMVP

0.87

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

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