Variant 8-8890522-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_004225.3(MFHAS1):c.2537C>G(p.Ala846Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0023 in 1,613,484 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 9 hom. )

Consequence

MFHAS1
NM_004225.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.48

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 Likely_benign. Variant got -5 ACMG points.

BP6

Variant 8-8890522-G-C is Benign according to our data. Variant chr8-8890522-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3060793.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFHAS1	NM_004225.3 linkuse as main transcript	c.2537C>G	p.Ala846Gly	missense_variant	1/3	ENST00000276282.7	NP_004216.2	Q9Y4C4
MFHAS1	XM_047422419.1 linkuse as main transcript	c.2537C>G	p.Ala846Gly	missense_variant	1/3		XP_047278375.1
MFHAS1	XM_011543852.4 linkuse as main transcript	c.2537C>G	p.Ala846Gly	missense_variant	1/2		XP_011542154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFHAS1	ENST00000276282.7 linkuse as main transcript	c.2537C>G	p.Ala846Gly	missense_variant	1/3	1	NM_004225.3	ENSP00000276282.6		Q9Y4C4

Frequencies

GnomAD3 genomes

AF:

0.00152

AC:

231

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00284

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00132

AC:

331

AN:

250722

Hom.:

AF XY:

0.00121

AC XY:

164

AN XY:

135540

show subpopulations

Gnomad AFR exome

AF:

0.000616

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.000143

Gnomad NFE exome

AF:

0.00257

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.00239

AC:

3486

AN:

1461104

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

1660

AN XY:

726862

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.000323

Gnomad4 NFE exome

AF:

0.00298

Gnomad4 OTH exome

AF:

0.00169

GnomAD4 genome

AF:

0.00152

AC:

232

AN:

152380

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00284

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00185

Hom.:

Bravo

AF:

0.00155

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00291

AC:

ExAC

AF:

0.00143

AC:

173

EpiCase

AF:

0.00251

EpiControl

AF:

0.00261

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MFHAS1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 06, 2022

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.051

Eigen

Benign

-0.051

Eigen_PC

Benign

0.060

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0036

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.3

REVEL

Benign

0.071

Sift

Benign

0.41

Sift4G

Uncertain

0.027

Polyphen

0.57

Vest4

0.51

MVP

0.62

MPC

0.25

ClinPred

0.026

GERP RS

4.2

Varity_R

0.079

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.25

Position offset: 1

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