Variant 16-56625862-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001363555.2(MT1E):c.11A>G(p.Asn4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000138 in 1,613,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

MT1E
NM_001363555.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.89

Variant links:

Genes affected

MT1E (HGNC:7397): (metallothionein 1E) Predicted to enable zinc ion binding activity. Involved in cellular response to cadmium ion and cellular response to zinc ion. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MT1E links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09566954).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MT1E	NM_001363555.2 linkuse as main transcript	c.11A>G	p.Asn4Ser	missense_variant	1/2	ENST00000330439.7	NP_001350484.1
MT1E	NM_175617.4 linkuse as main transcript	c.11A>G	p.Asn4Ser	missense_variant	1/3		NP_783316.2	P04732-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MT1E	ENST00000330439.7 linkuse as main transcript	c.11A>G	p.Asn4Ser	missense_variant	1/2	1	NM_001363555.2	ENSP00000328137.6	P04732-2
MT1E	ENST00000306061.10 linkuse as main transcript	c.11A>G	p.Asn4Ser	missense_variant	1/3	1		ENSP00000307706.5	P04732-1
MT1E	ENST00000568293.1 linkuse as main transcript	c.11A>G	p.Asn4Ser	missense_variant	1/2	2		ENSP00000457516.1	H3BU80

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000756

AC:

AN:

251470

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135916

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:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000142

AC:

208

AN:

1461412

Hom.:

Cov.:

AF XY:

0.000158

AC XY:

115

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000165

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000144

Hom.:

Bravo

AF:

0.0000793

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

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

Dec 26, 2023

The c.11A>G (p.N4S) alteration is located in exon 1 (coding exon 1) of the MT1E gene. This alteration results from a A to G substitution at nucleotide position 11, causing the asparagine (N) at amino acid position 4 to be replaced by a serine (S). 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

0.066

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.26

T;.;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.84

T;T;D

M_CAP

Benign

0.0063

MetaRNN

Benign

0.096

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.8

D;D;D

REVEL

Benign

0.053

Sift

Benign

0.099

T;D;D

Sift4G

Benign

0.38

T;T;D

Polyphen

0.18

B;.;P

Vest4

0.14

MVP

0.068

MPC

0.43

ClinPred

0.11

GERP RS

0.52

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.089

gMVP

0.029

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