22-46308683-C-T

Variant names:

• chr22-46308683-C-T
• rs34725504
• NM_016426.7:c.502C>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_016426.7(GTSE1):​c.502C>T​(p.Leu168Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,613,956 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (42 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (37 hom.)
• Consequence: GTSE1 NM_016426.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.14
• Publications: 4 publications found

Genes affected

GTSE1 (HGNC:13698): (G2 and S-phase expressed 1) The protein encoded by this gene is only expressed in the S and G2 phases of the cell cycle, where it colocalizes with cytoplasmic tubulin and microtubules. In response to DNA damage, the encoded protein accumulates in the nucleus and binds the tumor suppressor protein p53, shuttling it out of the nucleus and repressing its ability to induce apoptosis. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 22-46308683-C-T is Benign according to our data. Variant chr22-46308683-C-T is described in ClinVar as Benign. ClinVar VariationId is 777736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.14 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0118 (1791/152384) while in subpopulation AFR AF = 0.0408 (1697/41592). AF 95% confidence interval is 0.0392. There are 42 homozygotes in GnomAd4. There are 820 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 42 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016426.7. 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
	GTSE1	NM_016426.7	MANE Select	c.502C>T	p.Leu168Leu	synonymous	Exon 4 of 12	NP_057510.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTSE1	ENST00000454366.2	TSL:1 MANE Select	c.502C>T	p.Leu168Leu	synonymous	Exon 4 of 12	ENSP00000415430.1	Q9NYZ3
	GTSE1	ENST00000926492.1		c.502C>T	p.Leu168Leu	synonymous	Exon 4 of 12	ENSP00000596551.1
	GTSE1	ENST00000926491.1		c.502C>T	p.Leu168Leu	synonymous	Exon 4 of 11	ENSP00000596550.1

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1786 AN: 152266 Hom.: 41 Cov.: 33

Gnomad AFR AF: 0.0408

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00764

GnomAD2 exomes AF: 0.00302 AC: 756 AN: 250088 AF XY: 0.00219

Gnomad AFR exome AF: 0.0421

Gnomad AMR exome AF: 0.00182

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000888

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.00118 AC: 1723 AN: 1461572 Hom.: 37 Cov.: 33 AF XY: 0.00103 AC XY: 751 AN XY: 727074

African (AFR) AF: 0.0427 AC: 1431 AN: 33476

American (AMR) AF: 0.00217 AC: 97 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53122

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.0000333 AC: 37 AN: 1112002

Other (OTH) AF: 0.00253 AC: 153 AN: 60388

GnomAD4 genome AF: 0.0118 AC: 1791 AN: 152384 Hom.: 42 Cov.: 33 AF XY: 0.0110 AC XY: 820 AN XY: 74522

African (AFR) AF: 0.0408 AC: 1697 AN: 41592

American (AMR) AF: 0.00431 AC: 66 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

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

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68040

Other (OTH) AF: 0.00756 AC: 16 AN: 2116

Alfa AF: 0.00539 Hom.: 14

Bravo AF: 0.0131

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	-0.35
CADD	Benign	8.1
DANN	Benign	0.79
PhyloP100		1.1
Mutation Taster		=100/0	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: rs34725504; hg19: chr22-46704580;