chr8-8890391-A-C

Variant names:

• chr8-8890391-A-C
• NM_004225.3:c.2668T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004225.3(MFHAS1):​c.2668T>G​(p.Phe890Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MFHAS1 NM_004225.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.54
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFHAS1	NM_004225.3	c.2668T>G	p.Phe890Val	missense_variant	Exon 1 of 3	ENST00000276282.7	NP_004216.2
MFHAS1	XM_047422419.1	c.2668T>G	p.Phe890Val	missense_variant	Exon 1 of 3		XP_047278375.1
MFHAS1	XM_011543852.4	c.2668T>G	p.Phe890Val	missense_variant	Exon 1 of 2		XP_011542154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFHAS1	ENST00000276282.7	c.2668T>G	p.Phe890Val	missense_variant	Exon 1 of 3	1	NM_004225.3	ENSP00000276282.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 80

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2668T>G (p.F890V) alteration is located in exon 1 (coding exon 1) of the MFHAS1 gene. This alteration results from a T to G substitution at nucleotide position 2668, causing the phenylalanine (F) at amino acid position 890 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.039	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0079	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		6.5
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.22
Sift	Benign	0.31	T
Sift4G	Uncertain	0.011	D
Polyphen		0.80	P
Vest4		0.75
MutPred		0.53		Loss of stability (P = 0.2093);
MVP		0.61
MPC		0.47
ClinPred		0.77	D
GERP RS		5.0
Varity_R		0.30
gMVP		0.52
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

hg19: chr8-8747901;