rs2594458

Variant names:

• chr7-114945750-C-A
• rs2594458
• NM_001166345.3:c.217+3353C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-114945750-C-A
• chr7-114945750-C-G
• chr7-114945750-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001166345.3(MDFIC):​c.217+3353C>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MDFIC NM_001166345.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 2 publications found

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]

MDFIC Gene-Disease associations (from GenCC):

• lymphatic malformation 12

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDFIC	NM_001166345.3	c.217+3353C>A		intron_variant	Intron 3 of 4	ENST00000393486.6	NP_001159817.1
MDFIC	NM_199072.5	c.544+3353C>A		intron_variant	Intron 3 of 4		NP_951038.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDFIC	ENST00000393486.6	c.217+3353C>A		intron_variant	Intron 3 of 4	1	NM_001166345.3	ENSP00000377126.1
MDFIC	ENST00000427207.5	c.175+3353C>A		intron_variant	Intron 2 of 3	3		ENSP00000392098.1
MDFIC	ENST00000498196.1	c.52+3353C>A		intron_variant	Intron 2 of 3	4		ENSP00000418337.1
MDFIC	ENST00000431629.5	n.187+3353C>A		intron_variant	Intron 2 of 4	5		ENSP00000416668.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.7
DANN	Benign	0.49
PhyloP100		-0.031

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: rs2594458; hg19: chr7-114585805;