9-133031126-A-G

Variant names:

• chr9-133031126-A-G
• NM_012087.4:c.115A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012087.4(GTF3C5):​c.115A>G​(p.Met39Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GTF3C5 NM_012087.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.02

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF3C5	NM_012087.4	c.115A>G	p.Met39Val	missense_variant	Exon 1 of 11	ENST00000372097.10	NP_036219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF3C5	ENST00000372097.10	c.115A>G	p.Met39Val	missense_variant	Exon 1 of 11	1	NM_012087.4	ENSP00000361169.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.115A>G (p.M39V) alteration is located in exon 1 (coding exon 1) of the GTF3C5 gene. This alteration results from a A to G substitution at nucleotide position 115, causing the methionine (M) at amino acid position 39 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.094	T;.;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.071	D
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Benign	-0.55	T
MutationAssessor	Pathogenic	3.1	M;M;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.21
Sift	Uncertain	0.012	D;D;D
Sift4G	Uncertain	0.034	D;T;D
Polyphen		0.97	D;D;.
Vest4		0.54
MutPred		0.57		Gain of methylation at K38 (P = 0.0232);Gain of methylation at K38 (P = 0.0232);Gain of methylation at K38 (P = 0.0232);
MVP		0.56
MPC		1.2
ClinPred		0.98	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.85
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-135906513;