rs371595443

Variant names:

• chr2-27326698-G-A
• rs371595443
• NM_001035521.3:c.2713C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-27326698-G-A
• chr2-27326698-G-C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001035521.3(GTF3C2):​c.2713C>T​(p.His905Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: GTF3C2 NM_001035521.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.10
• Publications: 0 publications found

Genes affected

GTF3C2 (HGNC:4665): (general transcription factor IIIC subunit 2) Contributes to DNA binding activity. Involved in transcription by RNA polymerase III. Located in nucleoplasm. Part of transcription factor TFIIIC complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07562217).
• BS2: High AC in GnomAd4 at 11 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001035521.3. 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
	GTF3C2	NM_001035521.3	MANE Select	c.2713C>T	p.His905Tyr	missense	Exon 19 of 19	NP_001030598.1	Q8WUA4-1
	GTF3C2	NM_001318909.4		c.2713C>T	p.His905Tyr	missense	Exon 19 of 19	NP_001305838.2	Q8WUA4-1
	GTF3C2	NM_001388380.3		c.2713C>T	p.His905Tyr	missense	Exon 20 of 20	NP_001375309.2	Q8WUA4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF3C2	ENST00000264720.8	TSL:1 MANE Select	c.2713C>T	p.His905Tyr	missense	Exon 19 of 19	ENSP00000264720.3	Q8WUA4-1
	GTF3C2	ENST00000359541.6	TSL:1	c.2713C>T	p.His905Tyr	missense	Exon 19 of 19	ENSP00000352536.2	Q8WUA4-1
	GTF3C2	ENST00000454704.5	TSL:1	c.1237C>T	p.His413Tyr	missense	Exon 10 of 10	ENSP00000393429.1	H0Y4Q6

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000318 AC: 8 AN: 251226 AF XY: 0.0000221

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461660 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727152

African (AFR) AF: 0.000149 AC: 5 AN: 33478

American (AMR) AF: 0.000112 AC: 5 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111820

Other (OTH) AF: 0.0000166 AC: 1 AN: 60384

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74336

African (AFR) AF: 0.000217 AC: 9 AN: 41450

American (AMR) AF: 0.0000655 AC: 1 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.0000831

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.071
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.97	L
PhyloP100		3.1
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.70	N
REVEL	Uncertain	0.30
Sift	Benign	0.030	D
Sift4G	Benign	0.35	T
Polyphen		0.13	B
Vest4		0.21
MVP		0.59
MPC		0.19
ClinPred		0.047	T
GERP RS		4.4
Varity_R		0.058
gMVP		0.54
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs371595443; hg19: chr2-27549565;