7-115940911-AC-GT

Variant names:

• chr7-115940911-AC-GT
• NM_012252.4:c.683_684delGTinsAC
• TFEC p.Arg228His

Variant summary

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

The NM_012252.4(TFEC):​c.683_684delGTinsAC​(p.Arg228His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R228G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TFEC NM_012252.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94
• Publications: 0 publications found

Genes affected

TFEC (HGNC:11754): (transcription factor EC) This gene encodes a member of the micropthalmia (MiT) family of basic helix-loop-helix leucine zipper transcription factors. MiT transcription factors regulate the expression of target genes by binding to E-box recognition sequences as homo- or heterodimers, and play roles in multiple cellular processes including survival, growth and differentiation. The encoded protein is a transcriptional activator of the nonmuscle myosin II heavy chain-A gene, and may also co-regulate target genes in osteoclasts as a heterodimer with micropthalmia-associated transcription factor. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012252.4. 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
	TFEC	NM_012252.4	MANE Select	c.683_684delGTinsAC	p.Arg228His	missense	N/A	NP_036384.1	O14948-1
	TFEC	NM_001018058.3		c.596_597delGTinsAC	p.Arg199His	missense	N/A	NP_001018068.1	O14948-2
	TFEC	NM_001244583.2		c.482_483delGTinsAC	p.Arg161His	missense	N/A	NP_001231512.1	O14948-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFEC	ENST00000265440.12	TSL:1 MANE Select	c.683_684delGTinsAC	p.Arg228His	missense	N/A	ENSP00000265440.7	O14948-1
	TFEC	ENST00000320239.11	TSL:1	c.596_597delGTinsAC	p.Arg199His	missense	N/A	ENSP00000318676.7	O14948-2
	TFEC	ENST00000871199.1		c.683_684delGTinsAC	p.Arg228His	missense	N/A	ENSP00000541258.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-115580965;