rs1047844

Variant names:

• chr9-133043785-C-A
• rs1047844
• NM_012087.4:c.431C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-133043785-C-A
• chr9-133043785-C-G
• chr9-133043785-C-T

Variant summary

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

The NM_012087.4(GTF3C5):​c.431C>A​(p.Ser144*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GTF3C5 NM_012087.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.38
• 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: Ambry Genetics, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF3C5	NM_012087.4	MANE Select	c.431C>A	p.Ser144*	stop_gained	Exon 3 of 11	NP_036219.2
	GTF3C5	NM_001122823.2		c.431C>A	p.Ser144*	stop_gained	Exon 3 of 12	NP_001116295.1
	GTF3C5	NM_001286709.2		c.51-6998C>A		intron	N/A	NP_001273638.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF3C5	ENST00000372097.10	TSL:1 MANE Select	c.431C>A	p.Ser144*	stop_gained	Exon 3 of 11	ENSP00000361169.5
	GTF3C5	ENST00000372108.9	TSL:1	c.431C>A	p.Ser144*	stop_gained	Exon 3 of 12	ENSP00000361180.5
	GTF3C5	ENST00000342018.12	TSL:5	c.431C>A	p.Ser144*	stop_gained	Exon 3 of 11	ENSP00000339530.7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	39
DANN	Uncertain	1.0
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.99	D
PhyloP100		7.4
Vest4		0.42
GERP RS		5.0
Mutation Taster		=5/195	disease causing (fs/PTC)

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: rs1047844; hg19: chr9-135919172;