7-114923029-G-A

Variant names:

• chr7-114923029-G-A
• rs1410923033
• NM_001166345.3:c.-5G>A

Variant summary

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

The NM_199072.5(MDFIC):​c.323G>A​(p.Arg108Gln) 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. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MDFIC NM_199072.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.283
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Ambry Genetics

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=0.13776249).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199072.5. 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
	MDFIC	NM_001166345.3	MANE Select	c.-5G>A		5_prime_UTR	Exon 2 of 5	NP_001159817.1	Q9P1T7-2
	MDFIC	NM_199072.5		c.323G>A	p.Arg108Gln	missense	Exon 2 of 5	NP_951038.1	Q9P1T7-1
	MDFIC	NM_001166346.1		c.323G>A	p.Arg108Gln	missense	Exon 2 of 3	NP_001159818.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDFIC	ENST00000393486.6	TSL:1 MANE Select	c.-5G>A		5_prime_UTR	Exon 2 of 5	ENSP00000377126.1	Q9P1T7-2
	MDFIC	ENST00000423503.1	TSL:1	c.-5G>A		5_prime_UTR	Exon 1 of 2	ENSP00000401623.1	C9J104
	MDFIC	ENST00000963682.1		c.-5G>A		5_prime_UTR	Exon 2 of 6	ENSP00000633741.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 44178 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1227676 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 602848

African (AFR) AF: 0.00 AC: 0 AN: 23378

American (AMR) AF: 0.00 AC: 0 AN: 11100

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17560

East Asian (EAS) AF: 0.00 AC: 0 AN: 26608

South Asian (SAS) AF: 0.00 AC: 0 AN: 55068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3428

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 999244

Other (OTH) AF: 0.00 AC: 0 AN: 48932

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Uncertain	1.0
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.28
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.033
Sift	Benign	0.19	T
Sift4G	Benign	0.38	T
Vest4		0.16
MutPred		0.18		Loss of MoRF binding (P = 0.0444)
MVP		0.067
ClinPred		0.92	D
GERP RS		2.7
PromoterAI		-0.16	Neutral
gMVP		0.083

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: rs1410923033; hg19: chr7-114563084;