Variant 16-56659146-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_005949.4(MT1F):c.168G>C(p.Lys56Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000978 in 1,614,144 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 6 hom., cov: 33)

Exomes 𝑓: 0.00055 ( 11 hom. )

Consequence

MT1F
NM_005949.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.207

Variant links:

Genes affected

MT1F (HGNC:7398): (metallothionein 1F) Predicted to enable zinc ion binding activity. Involved in cellular response to cadmium ion. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MT1F links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008713752).

BP6

Variant 16-56659146-G-C is Benign according to our data. Variant chr16-56659146-G-C is described in ClinVar as [Benign]. Clinvar id is 791555.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00511 (779/152320) while in subpopulation AFR AF= 0.0174 (723/41558). AF 95% confidence interval is 0.0163. There are 6 homozygotes in gnomad4. There are 354 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MT1F	NM_005949.4 linkuse as main transcript	c.168G>C	p.Lys56Asn	missense_variant	3/3	ENST00000334350.7	NP_005940.1
MT1F	NM_001301272.2 linkuse as main transcript	c.*75G>C		3_prime_UTR_variant	3/3		NP_001288201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MT1F	ENST00000334350.7 linkuse as main transcript	c.168G>C	p.Lys56Asn	missense_variant	3/3	1	NM_005949.4	ENSP00000334872	P1
MT1F	ENST00000568475.1 linkuse as main transcript	c.*75G>C		3_prime_UTR_variant	3/3	2		ENSP00000456462
MT1F	ENST00000564295.1 linkuse as main transcript	n.1416G>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.00511

AC:

777

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00307

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:

0.0000441

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00134

AC:

336

AN:

251472

Hom.:

AF XY:

0.000927

AC XY:

126

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.0176

Gnomad AMR exome

AF:

0.000954

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000879

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000547

AC:

799

AN:

1461824

Hom.:

Cov.:

AF XY:

0.000469

AC XY:

341

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0189

Gnomad4 AMR exome

AF:

0.000984

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.00511

AC:

779

AN:

152320

Hom.:

Cov.:

AF XY:

0.00475

AC XY:

354

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0174

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000744

Hom.:

Bravo

AF:

0.00576

ESP6500AA

AF:

0.0157

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00155

AC:

188

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.30

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0087

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.59

D;N;N

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.032

Sift

Uncertain

0.025

Sift4G

Benign

0.14

Polyphen

0.32

Vest4

0.37

MutPred

0.38

Loss of methylation at K56 (P = 0.0013);

MVP

0.040

MPC

0.19

ClinPred

0.033

GERP RS

-0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.22

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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