Variant rs11643815 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032935.3(MT4):c.143G>A(p.Gly48Asp) variant causes a missense change. The variant allele was found at a frequency of 0.124 in 1,606,480 control chromosomes in the GnomAD database, including 13,519 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.098 ( 919 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12600 hom. )

Consequence

MT4
NM_032935.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.09

Variant links:

Genes affected

MT4 (HGNC:18705): (metallothionein 4) Predicted to enable metal ion binding activity. Predicted to be involved in cellular response to metal ion; cellular zinc ion homeostasis; and detoxification of copper ion. Predicted to act upstream of or within cellular metal ion homeostasis. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MT4 links:

BBS2 (HGNC:967): (Bardet-Biedl syndrome 2) This gene is a member of the Bardet-Biedl syndrome (BBS) gene family. Bardet-Biedl syndrome is an autosomal recessive disorder characterized by severe pigmentary retinopathy, obesity, polydactyly, renal malformation and cognitive disability. The proteins encoded by BBS gene family members are structurally diverse and the similar phenotypes exhibited by mutations in BBS gene family members is likely due to their shared roles in cilia formation and function. Many BBS proteins localize to the basal bodies, ciliary axonemes, and pericentriolar regions of cells. BBS proteins may also be involved in intracellular trafficking via microtubule-related transport. The protein encoded by this gene forms a multiprotein BBSome complex with seven other BBS proteins.[provided by RefSeq, Oct 2014]

BBS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003320247).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MT4	NM_032935.3 linkuse as main transcript	c.143G>A	p.Gly48Asp	missense_variant	3/3	ENST00000219162.4	NP_116324.2	P47944

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT4	ENST00000219162.4 linkuse as main transcript	c.143G>A	p.Gly48Asp	missense_variant	3/3	1	NM_032935.3	ENSP00000219162.3		P47944
BBS2	ENST00000682930.1 linkuse as main transcript	c.42+1789C>T		intron_variant				ENSP00000507981.1		A0A804HKL9

Frequencies

GnomAD3 genomes

AF:

0.0979

AC:

14885

AN:

152102

Hom.:

919

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0289

Gnomad AMI

AF:

0.250

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.00598

Gnomad SAS

AF:

0.0928

Gnomad FIN

AF:

0.100

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.0967

GnomAD3 exomes

AF:

0.108

AC:

26310

AN:

244600

Hom.:

1710

AF XY:

0.109

AC XY:

14433

AN XY:

132620

show subpopulations

Gnomad AFR exome

AF:

0.0270

Gnomad AMR exome

AF:

0.122

Gnomad ASJ exome

AF:

0.135

Gnomad EAS exome

AF:

0.00576

Gnomad SAS exome

AF:

0.0946

Gnomad FIN exome

AF:

0.103

Gnomad NFE exome

AF:

0.133

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.127

AC:

184656

AN:

1454260

Hom.:

12600

Cov.:

AF XY:

0.126

AC XY:

91445

AN XY:

723354

show subpopulations

Gnomad4 AFR exome

AF:

0.0237

Gnomad4 AMR exome

AF:

0.120

Gnomad4 ASJ exome

AF:

0.135

Gnomad4 EAS exome

AF:

0.00244

Gnomad4 SAS exome

AF:

0.0981

Gnomad4 FIN exome

AF:

0.103

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.111

GnomAD4 genome

AF:

0.0978

AC:

14881

AN:

152220

Hom.:

919

Cov.:

AF XY:

0.0950

AC XY:

7071

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0289

Gnomad4 AMR

AF:

0.100

Gnomad4 ASJ

AF:

0.144

Gnomad4 EAS

AF:

0.00599

Gnomad4 SAS

AF:

0.0929

Gnomad4 FIN

AF:

0.100

Gnomad4 NFE

AF:

0.142

Gnomad4 OTH

AF:

0.0952

Alfa

AF:

0.114

Hom.:

950

Bravo

AF:

0.0932

TwinsUK

AF:

0.146

AC:

541

ALSPAC

AF:

0.137

AC:

528

ESP6500AA

AF:

0.0292

AC:

128

ESP6500EA

AF:

0.132

AC:

1135

ExAC

AF:

0.109

AC:

13240

Asia WGS

AF:

0.0600

AC:

208

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.45

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0033

MetaSVM

Benign

-1.3

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-5.8

REVEL

Uncertain

0.33

Sift

Benign

0.13

Sift4G

Benign

0.19

Polyphen

1.0

Vest4

0.32

MPC

0.16

ClinPred

0.024

GERP RS

5.9

Varity_R

0.69

gMVP

0.28

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over