rs900805542

Variant names:

• chr7-114923125-A-C
• NM_001166345.3:c.92A>C

Your query was ambiguous. Multiple possible variants found:

• chr7-114923125-A-C
• chr7-114923125-A-G
• chr7-114923125-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001166345.3(MDFIC):​c.92A>C​(p.Gln31Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000732 in 1,366,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. Q31R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: MDFIC NM_001166345.3 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.493

Genes affected

MDFIC (HGNC:28870): (MyoD family inhibitor domain containing) This gene product is a member of a family of proteins characterized by a specific cysteine-rich C-terminal domain, which is involved in transcriptional regulation of viral genome expression. Alternative translation initiation from an upstream non-AUG (GUG), and an in-frame, downstream AUG codon, results in the production of two isoforms, p40 and p32, respectively, which have different subcellular localization; p32 is mainly found in the cytoplasm, whereas p40 is targeted to the nucleolus. Both isoforms have transcriptional regulatory activity that is attributable to the cysteine-rich C-terminal domain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07589269).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDFIC	NM_001166345.3	c.92A>C	p.Gln31Pro	missense_variant, splice_region_variant	Exon 2 of 5	ENST00000393486.6	NP_001159817.1
MDFIC	NM_199072.5	c.419A>C	p.Gln140Pro	missense_variant, splice_region_variant	Exon 2 of 5		NP_951038.1
MDFIC	NM_001166346.1	c.419A>C	p.Gln140Pro	missense_variant, splice_region_variant	Exon 2 of 3		NP_001159818.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDFIC	ENST00000393486.6	c.92A>C	p.Gln31Pro	missense_variant, splice_region_variant	Exon 2 of 5	1	NM_001166345.3	ENSP00000377126.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.32e-7 AC: 1 AN: 1366902 Hom.: 0 Cov.: 32 AF XY: 0.00000148 AC XY: 1 AN XY: 674720

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.36e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.076	.;T;.;T;T;.
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.44	T;T;T;.;T;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.076	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	.;L;.;.;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.35	N;N;.;D;D;N
REVEL	Benign	0.076
Sift	Benign	0.081	T;T;.;D;D;T
Sift4G	Benign	0.35	T;T;T;D;D;T
Polyphen		0.073	.;B;.;.;.;.
Vest4		0.30
MutPred		0.12		.;Gain of glycosylation at S28 (P = 0.0583);.;Gain of glycosylation at S28 (P = 0.0583);Gain of glycosylation at S28 (P = 0.0583);.;
MVP		0.21
ClinPred		0.10	T
GERP RS		-0.77
Varity_R		0.093
gMVP		0.098

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-114563180;