Genetic Variant NM_001282446.2:c.311G>A (chr7-39609676-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001282446.2(YAE1):c.311G>A(p.Gly104Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,535,508 control chromosomes in the GnomAD database, including 35,207 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 7232 hom., cov: 33)

Exomes 𝑓: 0.19 ( 27975 hom. )

Consequence

YAE1
NM_001282446.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.21

Publications

14 publications found

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:

ENSG00000231951 (HGNC:):

ENSG00000231951 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1658371E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YAE1	NM_001282446.2 link	c.311G>A	p.Gly104Glu	missense_variant	Exon 3 of 3		NP_001269375.1	Q9NRH1-2
LOC646999		n.39609676G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
YAE1	ENST00000432096.3 link	c.311G>A	p.Gly104Glu	missense_variant	Exon 3 of 3	2	ENSP00000395777.2	Q9NRH1-2
ENSG00000231951	ENST00000420748.1 link	n.499C>T		non_coding_transcript_exon_variant	Exon 2 of 2	4
ENSG00000106540	ENST00000446267.1 link	n.-41G>A		upstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

41090

AN:

152064

Hom.:

7206

Cov.:

show subpopulations

Gnomad AFR

AF:

0.503

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.230

GnomAD2 exomes

AF:

0.196

AC:

25628

AN:

130650

AF XY:

0.187

show subpopulations

Gnomad AFR exome

AF:

0.514

Gnomad AMR exome

AF:

0.244

Gnomad ASJ exome

AF:

0.144

Gnomad EAS exome

AF:

0.127

Gnomad FIN exome

AF:

0.149

Gnomad NFE exome

AF:

0.190

Gnomad OTH exome

AF:

0.184

GnomAD4 exome

AF:

0.193

AC:

267045

AN:

1383326

Hom.:

27975

Cov.:

AF XY:

0.190

AC XY:

129841

AN XY:

682550

show subpopulations

African (AFR)

AF:

0.509

AC:

16093

AN:

31592

American (AMR)

AF:

0.247

AC:

8834

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

3525

AN:

25180

East Asian (EAS)

AF:

0.117

AC:

4169

AN:

35732

South Asian (SAS)

AF:

0.136

AC:

10800

AN:

79234

European-Finnish (FIN)

AF:

0.153

AC:

5123

AN:

33468

Middle Eastern (MID)

AF:

0.150

AC:

855

AN:

5692

European-Non Finnish (NFE)

AF:

0.191

AC:

206332

AN:

1078836

Other (OTH)

AF:

0.195

AC:

11314

AN:

57892

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

13701

27401

41102

54802

68503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7474

14948

22422

29896

37370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.271

AC:

41167

AN:

152182

Hom.:

7232

Cov.:

AF XY:

0.265

AC XY:

19750

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.503

AC:

20881

AN:

41504

American (AMR)

AF:

0.238

AC:

3637

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

485

AN:

3468

East Asian (EAS)

AF:

0.114

AC:

587

AN:

5164

South Asian (SAS)

AF:

0.137

AC:

661

AN:

4824

European-Finnish (FIN)

AF:

0.153

AC:

1622

AN:

10616

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.185

AC:

12563

AN:

67994

Other (OTH)

AF:

0.227

AC:

480

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1387

2775

4162

5550

6937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

392

784

1176

1568

1960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.177

Hom.:

1617

Bravo

AF:

0.289

TwinsUK

AF:

0.190

AC:

704

ALSPAC

AF:

0.182

AC:

700

ExAC

AF:

0.132

AC:

1827

Asia WGS

AF:

0.150

AC:

521

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.2

(source)

DANN

Benign

0.84

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.00030

LIST_S2

Benign

0.26

MetaRNN

Benign

0.00012

MetaSVM

Benign

-0.93

PhyloP100

-1.2

PROVEAN

Benign

0.58

REVEL

Benign

0.024

Sift

Benign

0.18

Sift4G

Benign

1.0

Vest4

0.012

ClinPred

0.0019

GERP RS

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over