Variant 7-39566437-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_020192.5(YAE1):c.19G>A(p.Ala7Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000269 in 1,614,168 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 4 hom. )

Consequence

YAE1
NM_020192.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.204

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:

YAE1 (HGNC:):

YAE1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0089279115).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YAE1	NM_020192.5 linkuse as main transcript	c.19G>A	p.Ala7Thr	missense_variant	1/3	ENST00000223273.7	NP_064577.1	Q9NRH1-1
YAE1	NM_001282446.2 linkuse as main transcript	c.19G>A	p.Ala7Thr	missense_variant	1/3		NP_001269375.1	Q9NRH1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
YAE1	ENST00000223273.7 linkuse as main transcript	c.19G>A	p.Ala7Thr	missense_variant	1/3	1	NM_020192.5	ENSP00000223273.2	Q9NRH1-1
YAE1	ENST00000432096.2 linkuse as main transcript	c.19G>A	p.Ala7Thr	missense_variant	1/3	2		ENSP00000395777.2	Q9NRH1-2
YAE1	ENST00000448268.5 linkuse as main transcript	c.19G>A	p.Ala7Thr	missense_variant	1/3	2		ENSP00000400511.1	C9IZ57
YAE1	ENST00000474392.1 linkuse as main transcript	n.53G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000263

AC:

AN:

251384

Hom.:

AF XY:

0.000294

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000276

AC:

404

AN:

1461814

Hom.:

Cov.:

AF XY:

0.000286

AC XY:

208

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00112

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000258

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000197

AC:

AN:

152354

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000179

Hom.:

Bravo

AF:

0.000215

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000264

AC:

EpiCase

AF:

0.0000545

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 14, 2023

The c.19G>A (p.A7T) alteration is located in exon 1 (coding exon 1) of the YAE1D1 gene. This alteration results from a G to A substitution at nucleotide position 19, causing the alanine (A) at amino acid position 7 to be replaced by a threonine (T). 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

0.087

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0058

T;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.61

T;T;T

M_CAP

Benign

0.0068

MetaRNN

Benign

0.0089

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.029

Sift

Benign

0.24

T;T;T

Sift4G

Benign

0.32

T;T;T

Polyphen

0.0030

B;.;.

Vest4

0.095

MVP

0.014

MPC

0.13

ClinPred

0.014

GERP RS

-7.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.044

gMVP

0.53

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