Variant rs2298847 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 4P and 8B. PVS1_StrongBA1

The NM_001301267.2(MT1G):c.29-2A>T variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,613,798 control chromosomes in the GnomAD database, including 19,757 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 2309 hom., cov: 33)

Exomes 𝑓: 0.14 ( 17448 hom. )

Consequence

MT1G
NM_001301267.2 splice_acceptor, intron

Scores

Splicing: ADA: 0.00001695

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.11

Variant links:

Genes affected

MT1G (HGNC:7399): (metallothionein 1G) Enables zinc ion binding activity. Involved in cellular response to metal ion; cellular response to vascular endothelial growth factor stimulus; and negative regulation of growth. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MT1G links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.35978836 fraction of the gene. Cryptic splice site detected, with MaxEntScore 12, offset of 3, new splice context is: ggctttttctcttcttgcAGgtg. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MT1G	NM_001301267.2 link	c.29-2A>T		splice_acceptor_variant, intron_variant		ENST00000379811.4	NP_001288196.1	P13640-1
MT1G	NM_005950.3 link	c.29-5A>T		splice_region_variant, intron_variant			NP_005941.1	P13640-2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MT1G	ENST00000379811.4 link	c.29-2A>T	splice_acceptor_variant, intron_variant	1	NM_001301267.2	ENSP00000369139.4	P13640-1
MT1G	ENST00000444837.6 link	c.29-5A>T	splice_region_variant, intron_variant	1		ENSP00000391397.2	P13640-2
MT1G	ENST00000568675.1 link	n.57-5A>T	splice_region_variant, intron_variant	1
MT1G	ENST00000569500.5 link	c.29-412A>T	intron_variant	3		ENSP00000456675.1	H3BSF1

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23407

AN:

152028

Hom.:

2308

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.284

Gnomad ASJ

AF:

0.148

Gnomad EAS

AF:

0.413

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.151

GnomAD3 exomes

AF:

0.191

AC:

47948

AN:

251082

Hom.:

6526

AF XY:

0.183

AC XY:

24878

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.155

Gnomad AMR exome

AF:

0.396

Gnomad ASJ exome

AF:

0.145

Gnomad EAS exome

AF:

0.420

Gnomad SAS exome

AF:

0.237

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.149

GnomAD4 exome

AF:

0.136

AC:

198273

AN:

1461652

Hom.:

17448

Cov.:

AF XY:

0.137

AC XY:

99600

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.149

Gnomad4 AMR exome

AF:

0.381

Gnomad4 ASJ exome

AF:

0.141

Gnomad4 EAS exome

AF:

0.381

Gnomad4 SAS exome

AF:

0.236

Gnomad4 FIN exome

AF:

0.106

Gnomad4 NFE exome

AF:

0.109

Gnomad4 OTH exome

AF:

0.150

GnomAD4 genome

AF:

0.154

AC:

23425

AN:

152146

Hom.:

2309

Cov.:

AF XY:

0.160

AC XY:

11894

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.151

Gnomad4 AMR

AF:

0.285

Gnomad4 ASJ

AF:

0.148

Gnomad4 EAS

AF:

0.413

Gnomad4 SAS

AF:

0.233

Gnomad4 FIN

AF:

0.104

Gnomad4 NFE

AF:

0.111

Gnomad4 OTH

AF:

0.154

Alfa

AF:

0.121

Hom.:

401

Bravo

AF:

0.167

TwinsUK

AF:

0.0976

AC:

362

ALSPAC

AF:

0.109

AC:

419

ESP6500AA

AF:

0.155

AC:

682

ESP6500EA

AF:

0.115

AC:

988

ExAC

AF:

0.182

AC:

22120

Asia WGS

AF:

0.296

AC:

1031

AN:

3478

EpiCase

AF:

0.109

EpiControl

AF:

0.111

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.89

CADD

Benign

6.0

DANN

Benign

0.53

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.0074

GERP RS

-1.9

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000017

SpliceAI score (max)

0.32

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.32

Position offset: 23

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