Variant 8-144105743-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032272.5(MAF1):c.60T>C(p.Thr20=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.991 in 1,613,182 control chromosomes in the GnomAD database, including 793,581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.95 ( 69707 hom., cov: 30)

Exomes 𝑓: 1.0 ( 723874 hom. )

Consequence

MAF1
NM_032272.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.91

Variant links:

Genes affected

MAF1 (HGNC:24966): (MAF1 homolog, negative regulator of RNA polymerase III) This gene encodes a protein that is similar to Maf1, a Saccharomyces cerevisiae protein highly conserved in eukaryotic cells. Yeast Maf1 is a negative effector of RNA polymerase III (Pol III). It responds to changes in the cellular environment and represses pol III transcription. Biochemical studies identified the initiation factor TFIIIB as a target for Maf1-dependent repression. [provided by RefSeq, Jul 2008]

MAF1 links:

SHARPIN (HGNC:25321): (SHANK associated RH domain interactor) Enables polyubiquitin modification-dependent protein binding activity. Involved in protein linear polyubiquitination and regulation of signal transduction. Located in cytosol. Part of LUBAC complex. [provided by Alliance of Genome Resources, Apr 2022]

SHARPIN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 8-144105743-T-C is Benign according to our data. Variant chr8-144105743-T-C is described in ClinVar as [Benign]. Clinvar id is 403435.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.91 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAF1	NM_032272.5 linkuse as main transcript	c.60T>C	p.Thr20=	synonymous_variant	2/8	ENST00000322428.10	NP_115648.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAF1	ENST00000322428.10 linkuse as main transcript	c.60T>C	p.Thr20=	synonymous_variant	2/8	1	NM_032272.5	ENSP00000318604	P1

Frequencies

GnomAD3 genomes

AF:

0.954

AC:

145091

AN:

152066

Hom.:

69654

Cov.:

show subpopulations

Gnomad AFR

AF:

0.841

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.982

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.975

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.967

GnomAD3 exomes

AF:

0.988

AC:

248129

AN:

251182

Hom.:

122772

AF XY:

0.991

AC XY:

134603

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.838

Gnomad AMR exome

AF:

0.992

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.994

GnomAD4 exome

AF:

0.995

AC:

1453866

AN:

1460998

Hom.:

723874

Cov.:

AF XY:

0.996

AC XY:

723654

AN XY:

726792

show subpopulations

Gnomad4 AFR exome

AF:

0.833

Gnomad4 AMR exome

AF:

0.991

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.989

GnomAD4 genome

AF:

0.954

AC:

145201

AN:

152184

Hom.:

69707

Cov.:

AF XY:

0.956

AC XY:

71122

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.841

Gnomad4 AMR

AF:

0.982

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.968

Alfa

AF:

0.987

Hom.:

67383

Bravo

AF:

0.947

Asia WGS

AF:

0.991

AC:

3448

AN:

3478

EpiCase

AF:

0.999

EpiControl

AF:

0.999

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.031

DANN

Benign

0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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