9-133031051-GTC-ATA

Variant names:

• chr9-133031051-GTC-ATA
• NM_012087.4:c.40_42delGTCinsATA
• GTF3C5 p.Val14Ile

Variant summary

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

The NM_012087.4(GTF3C5):​c.40_42delGTCinsATA​(p.Val14Ile) 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 Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GTF3C5 NM_012087.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.407
• Publications: 0 publications found

Genes affected

GTF3C5 (HGNC:4668): (general transcription factor IIIC subunit 5) Predicted to contribute to DNA binding activity. Predicted to be involved in 5S class rRNA transcription by RNA polymerase III and tRNA transcription by RNA polymerase III. Predicted to act upstream of or within skeletal muscle cell differentiation. Located in nucleoplasm. Part of transcription factor TFIIIC complex. [provided by Alliance of Genome Resources, Apr 2022]

GTF3C5 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: G2P, Ambry Genetics

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012087.4. 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
	GTF3C5	NM_012087.4	MANE Select	c.40_42delGTCinsATA	p.Val14Ile	missense	N/A	NP_036219.2	Q9Y5Q8-1
	GTF3C5	NM_001122823.2		c.40_42delGTCinsATA	p.Val14Ile	missense	N/A	NP_001116295.1	Q9Y5Q8-3
	GTF3C5	NM_001286709.2		c.-64_-62delGTCinsATA		5_prime_UTR	Exon 1 of 9	NP_001273638.1	H7BY84

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF3C5	ENST00000372097.10	TSL:1 MANE Select	c.40_42delGTCinsATA	p.Val14Ile	missense	N/A	ENSP00000361169.5	Q9Y5Q8-1
	GTF3C5	ENST00000372108.9	TSL:1	c.40_42delGTCinsATA	p.Val14Ile	missense	N/A	ENSP00000361180.5	Q9Y5Q8-3
	GTF3C5	ENST00000916424.1		c.40_42delGTCinsATA	p.Val14Ile	missense	N/A	ENSP00000586483.1

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		0.41

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: chr9-135906438;