Variant 8-8890548-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_004225.3(MFHAS1):c.2511G>A(p.Lys837Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,613,534 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 10 hom. )

Consequence

MFHAS1
NM_004225.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.567

Variant links:

Genes affected

MFHAS1 (HGNC:16982): (multifunctional ROCO family signaling regulator 1) Identified in a human 8p amplicon, this gene is a potential oncogene whose expression is enhanced in some malignant fibrous histiocytomas (MFH). The primary structure of its product includes an ATP/GTP-binding site, three leucine zipper domains, and a leucine-rich tandem repeat, which are structural or functional elements for interactions among proteins related to the cell cycle, and which suggest that overexpression might be oncogenic with respect to MFH. [provided by RefSeq, Jul 2008]

MFHAS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 8-8890548-C-T is Benign according to our data. Variant chr8-8890548-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2658376.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.567 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFHAS1	NM_004225.3 link	c.2511G>A	p.Lys837Lys	synonymous_variant	1/3	ENST00000276282.7	NP_004216.2	Q9Y4C4
MFHAS1	XM_047422419.1 link	c.2511G>A	p.Lys837Lys	synonymous_variant	1/3		XP_047278375.1
MFHAS1	XM_011543852.4 link	c.2511G>A	p.Lys837Lys	synonymous_variant	1/2		XP_011542154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFHAS1	ENST00000276282.7 link	c.2511G>A	p.Lys837Lys	synonymous_variant	1/3	1	NM_004225.3	ENSP00000276282.6		Q9Y4C4

Frequencies

GnomAD3 genomes

AF:

0.00171

AC:

260

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000981

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00496

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00284

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00195

AC:

490

AN:

250754

Hom.:

AF XY:

0.00221

AC XY:

299

AN XY:

135562

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00203

Gnomad FIN exome

AF:

0.000664

Gnomad NFE exome

AF:

0.00314

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00283

AC:

4133

AN:

1461168

Hom.:

Cov.:

AF XY:

0.00288

AC XY:

2091

AN XY:

726894

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00255

Gnomad4 FIN exome

AF:

0.00106

Gnomad4 NFE exome

AF:

0.00331

Gnomad4 OTH exome

AF:

0.00187

GnomAD4 genome

AF:

0.00169

AC:

258

AN:

152366

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

122

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00455

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00284

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00203

Hom.:

Bravo

AF:

0.00139

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00273

EpiControl

AF:

0.00213

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MFHAS1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 01, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

MFHAS1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

9.1

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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