NM_005513.3:c.1068C>T

Variant names:

• chr3-120781218-C-T
• rs17243695
• NM_005513.3:c.1068C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_005513.3(GTF2E1):​c.1068C>T​(p.Ser356Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,614,104 control chromosomes in the GnomAD database, including 141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0094 (3 hom., cov: 32)
  • Exomes 𝑓: 0.013 (138 hom.)
• Consequence: GTF2E1 NM_005513.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.271
• Publications: 4 publications found

Genes affected

GTF2E1 (HGNC:4650): (general transcription factor IIE subunit 1) Enables RNA polymerase II general transcription initiation factor activity. Involved in transcription by RNA polymerase II. Located in cytosol and nucleoplasm. Part of transcription factor TFIID complex and transcription preinitiation complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 3-120781218-C-T is Benign according to our data. Variant chr3-120781218-C-T is described in ClinVar as Benign. ClinVar VariationId is 789165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.271 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0129 (18861/1461824) while in subpopulation MID AF = 0.0371 (214/5768). AF 95% confidence interval is 0.033. There are 138 homozygotes in GnomAdExome4. There are 9279 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1439 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005513.3. 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
	GTF2E1	NM_005513.3	MANE Select	c.1068C>T	p.Ser356Ser	synonymous	Exon 5 of 5	NP_005504.2	P29083

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2E1	ENST00000283875.6	TSL:1 MANE Select	c.1068C>T	p.Ser356Ser	synonymous	Exon 5 of 5	ENSP00000283875.5	P29083
	GTF2E1	ENST00000881964.1		c.1068C>T	p.Ser356Ser	synonymous	Exon 6 of 6	ENSP00000552023.1
	GTF2E1	ENST00000881966.1		c.1068C>T	p.Ser356Ser	synonymous	Exon 5 of 5	ENSP00000552025.1

Frequencies

GnomAD3 genomes AF: 0.00947 AC: 1441 AN: 152160 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00420

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00989

Gnomad ASJ AF: 0.0132

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0146

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00932 AC: 2337 AN: 250884 AF XY: 0.00946

Gnomad AFR exome AF: 0.00308

Gnomad AMR exome AF: 0.0101

Gnomad ASJ exome AF: 0.0154

Gnomad EAS exome AF: 0.000544

Gnomad FIN exome AF: 0.00171

Gnomad NFE exome AF: 0.0135

Gnomad OTH exome AF: 0.0131

GnomAD4 exome AF: 0.0129 AC: 18861 AN: 1461824 Hom.: 138 Cov.: 32 AF XY: 0.0128 AC XY: 9279 AN XY: 727214

African (AFR) AF: 0.00335 AC: 112 AN: 33480

American (AMR) AF: 0.0104 AC: 465 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 416 AN: 26134

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39694

South Asian (SAS) AF: 0.00480 AC: 414 AN: 86256

European-Finnish (FIN) AF: 0.00161 AC: 86 AN: 53418

Middle Eastern (MID) AF: 0.0371 AC: 214 AN: 5768

European-Non Finnish (NFE) AF: 0.0147 AC: 16310 AN: 1111956

Other (OTH) AF: 0.0138 AC: 836 AN: 60394

GnomAD4 genome AF: 0.00945 AC: 1439 AN: 152280 Hom.: 3 Cov.: 32 AF XY: 0.00848 AC XY: 631 AN XY: 74444

African (AFR) AF: 0.00419 AC: 174 AN: 41542

American (AMR) AF: 0.00987 AC: 151 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0132 AC: 46 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00538 AC: 26 AN: 4830

European-Finnish (FIN) AF: 0.000754 AC: 8 AN: 10616

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0146 AC: 992 AN: 68032

Other (OTH) AF: 0.0128 AC: 27 AN: 2110

Alfa AF: 0.0129 Hom.: 4

Bravo AF: 0.0104

Asia WGS AF: 0.00375 AC: 14 AN: 3478

EpiCase AF: 0.0166

EpiControl AF: 0.0161

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	6.2
DANN	Benign	0.88
PhyloP100		0.27
Mutation Taster		=98/2	polymorphism

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: rs17243695; hg19: chr3-120500065; COSMIC: COSV99381826; COSMIC: COSV99381826;