7-114942378-G-T

Variant names:

• chr7-114942378-G-T
• rs138487145
• NM_001166345.3:c.198G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001166345.3(MDFIC):​c.198G>T​(p.Ser66Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,448,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S66S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: MDFIC NM_001166345.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=0.157 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDFIC	NM_001166345.3	c.198G>T	p.Ser66Ser	synonymous_variant	Exon 3 of 5	ENST00000393486.6	NP_001159817.1
MDFIC	NM_199072.5	c.525G>T	p.Ser175Ser	synonymous_variant	Exon 3 of 5		NP_951038.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDFIC	ENST00000393486.6	c.198G>T	p.Ser66Ser	synonymous_variant	Exon 3 of 5	1	NM_001166345.3	ENSP00000377126.1
MDFIC	ENST00000427207.5	c.156G>T	p.Ser52Ser	synonymous_variant	Exon 2 of 4	3		ENSP00000392098.1
MDFIC	ENST00000498196.1	c.33G>T	p.Ser11Ser	synonymous_variant	Exon 2 of 4	4		ENSP00000418337.1
MDFIC	ENST00000431629.5	n.168G>T		non_coding_transcript_exon_variant	Exon 2 of 5	5		ENSP00000416668.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000276 AC: 4 AN: 1448592 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 720406

African (AFR) AF: 0.00 AC: 0 AN: 32806

American (AMR) AF: 0.00 AC: 0 AN: 42920

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25766

East Asian (EAS) AF: 0.00 AC: 0 AN: 39260

South Asian (SAS) AF: 0.00 AC: 0 AN: 83392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.00000362 AC: 4 AN: 1105952

Other (OTH) AF: 0.00 AC: 0 AN: 59792

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.52
DANN	Benign	0.41
PhyloP100		0.16

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

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Other links and lift over

dbSNP: rs138487145; hg19: chr7-114582433;