chr6-41646256-C-T

Variant names:

• chr6-41646256-C-T
• rs139421635
• NM_005586.4:c.207C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_005586.4(MDFI):​c.207C>T​(p.Ile69Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,569,306 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00087 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (1 hom.)
• Consequence: MDFI NM_005586.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.191
• 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 6-41646256-C-T is Benign according to our data. Variant chr6-41646256-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 779248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.191 with no splicing effect.

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.207C>T	p.Ile69Ile	synonymous	Exon 3 of 5	NP_005577.1	Q99750
	MDFI	NM_001300804.2		c.207C>T	p.Ile69Ile	synonymous	Exon 4 of 6	NP_001287733.1	Q99750
	MDFI	NM_001300806.2		c.207C>T	p.Ile69Ile	synonymous	Exon 2 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.207C>T	p.Ile69Ile	synonymous	Exon 3 of 5	ENSP00000230321.6	Q99750
	MDFI	ENST00000373051.6	TSL:5	c.207C>T	p.Ile69Ile	synonymous	Exon 3 of 5	ENSP00000362142.2	Q99750
	MDFI	ENST00000909785.1		c.207C>T	p.Ile69Ile	synonymous	Exon 3 of 5	ENSP00000579844.1

Frequencies

GnomAD3 genomes AF: 0.000868 AC: 132 AN: 152150 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00146

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000740 AC: 154 AN: 208052 AF XY: 0.000839

Gnomad AFR exome AF: 0.000350

Gnomad AMR exome AF: 0.000506

Gnomad ASJ exome AF: 0.000128

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000485

Gnomad NFE exome AF: 0.00132

Gnomad OTH exome AF: 0.000631

GnomAD4 exome AF: 0.00131 AC: 1862 AN: 1417038 Hom.: 1 Cov.: 31 AF XY: 0.00124 AC XY: 872 AN XY: 703596

African (AFR) AF: 0.000223 AC: 7 AN: 31438

American (AMR) AF: 0.000647 AC: 24 AN: 37116

Ashkenazi Jewish (ASJ) AF: 0.000123 AC: 3 AN: 24318

East Asian (EAS) AF: 0.00 AC: 0 AN: 36542

South Asian (SAS) AF: 0.0000756 AC: 6 AN: 79410

European-Finnish (FIN) AF: 0.0000379 AC: 2 AN: 52716

Middle Eastern (MID) AF: 0.000178 AC: 1 AN: 5610

European-Non Finnish (NFE) AF: 0.00161 AC: 1757 AN: 1091382

Other (OTH) AF: 0.00106 AC: 62 AN: 58506

GnomAD4 genome AF: 0.000867 AC: 132 AN: 152268 Hom.: 0 Cov.: 33 AF XY: 0.000766 AC XY: 57 AN XY: 74458

African (AFR) AF: 0.000337 AC: 14 AN: 41552

American (AMR) AF: 0.000849 AC: 13 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00146 AC: 99 AN: 68008

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000359 Hom.: 0

Bravo AF: 0.000956

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	4.6
DANN	Benign	0.70
PhyloP100		0.19
Mutation Taster		=100/0	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: rs139421635; hg19: chr6-41613994;