Variant 7-39572480-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020192.5(YAE1):c.455T>C(p.Ile152Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000582 in 1,613,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000061 ( 0 hom. )

Consequence

YAE1
NM_020192.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.64

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008905888).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YAE1	NM_020192.5 linkuse as main transcript	c.455T>C	p.Ile152Thr	missense_variant	3/3	ENST00000223273.7	NP_064577.1	Q9NRH1-1
YAE1	NM_001282446.2 linkuse as main transcript	c.251+1853T>C		intron_variant			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.455T>C	p.Ile152Thr	missense_variant	3/3	1	NM_020192.5	ENSP00000223273.2	Q9NRH1-1
YAE1	ENST00000448268.5 linkuse as main transcript	c.*114T>C		3_prime_UTR_variant	3/3	2		ENSP00000400511.1	C9IZ57
YAE1	ENST00000432096.2 linkuse as main transcript	c.251+1853T>C		intron_variant		2		ENSP00000395777.2	Q9NRH1-2
YAE1	ENST00000485025.1 linkuse as main transcript	n.578T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152186

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:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000115

AC:

AN:

251414

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000849

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000609

AC:

AN:

1461808

Hom.:

Cov.:

AF XY:

0.0000825

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000951

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74348

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:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000988

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

May 29, 2024

The c.455T>C (p.I152T) alteration is located in exon 3 (coding exon 3) of the YAE1D1 gene. This alteration results from a T to C substitution at nucleotide position 455, causing the isoleucine (I) at amino acid position 152 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

0.053

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.95

DANN

Benign

0.60

DEOGEN2

Benign

0.0027

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.38

M_CAP

Benign

0.0033

MetaRNN

Benign

0.0089

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.28

REVEL

Benign

0.016

Sift

Benign

0.39

Sift4G

Benign

0.57

Polyphen

0.0

Vest4

0.027

MVP

0.067

MPC

0.17

ClinPred

0.018

GERP RS

-7.6

Varity_R

0.019

gMVP

0.099

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