rs150152866

Variant names:

• chr6-41649706-C-G
• rs150152866
• NM_005586.4:c.347C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-41649706-C-G
• chr6-41649706-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005586.4(MDFI):​c.347C>G​(p.Ala116Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A116T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MDFI NM_005586.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 1 publications found

Genes affected

MDFI (HGNC:6967): (MyoD family inhibitor) This protein is a transcription factor that negatively regulates other myogenic family proteins. Studies of the mouse homolog, I-mf, show that it interferes with myogenic factor function by masking nuclear localization signals and preventing DNA binding. Knockout mouse studies show defects in the formation of vertebrae and ribs that also involve cartilage formation in these structures. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14373967).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005586.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDFI	NM_005586.4	MANE Select	c.347C>G	p.Ala116Gly	missense	Exon 4 of 5	NP_005577.1	Q99750
	MDFI	NM_001300804.2		c.347C>G	p.Ala116Gly	missense	Exon 5 of 6	NP_001287733.1	Q99750
	MDFI	NM_001300806.2		c.347C>G	p.Ala116Gly	missense	Exon 3 of 4	NP_001287735.1	Q99750

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDFI	ENST00000230321.11	TSL:1 MANE Select	c.347C>G	p.Ala116Gly	missense	Exon 4 of 5	ENSP00000230321.6	Q99750
	MDFI	ENST00000373051.6	TSL:5	c.347C>G	p.Ala116Gly	missense	Exon 4 of 5	ENSP00000362142.2	Q99750
	MDFI	ENST00000909785.1		c.347C>G	p.Ala116Gly	missense	Exon 4 of 5	ENSP00000579844.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.3
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.037
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.12	T
Polyphen		0.49	P
Vest4		0.15
MutPred		0.28		Gain of relative solvent accessibility (P = 0.0023)
MVP		0.39
MPC		0.22
ClinPred		0.53	D
GERP RS		4.7
Varity_R		0.11
Mutation Taster		=93/7	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

dbSNP: rs150152866; hg19: chr6-41617444;