22-46308502-A-G

Variant names:

• chr22-46308502-A-G
• rs202151215
• NM_016426.7:c.321A>G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_016426.7(GTSE1):​c.321A>G​(p.Leu107Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GTSE1 NM_016426.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-0.018 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTSE1	NM_016426.7	c.321A>G	p.Leu107Leu	synonymous_variant	Exon 4 of 12	ENST00000454366.2	NP_057510.5
GTSE1	XM_047441391.1	c.321A>G	p.Leu107Leu	synonymous_variant	Exon 3 of 11		XP_047297347.1
GTSE1	XM_047441392.1	c.321A>G	p.Leu107Leu	synonymous_variant	Exon 4 of 10		XP_047297348.1
GTSE1	XR_007067974.1	n.404A>G		non_coding_transcript_exon_variant	Exon 4 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTSE1	ENST00000454366.2	c.321A>G	p.Leu107Leu	synonymous_variant	Exon 4 of 12	1	NM_016426.7	ENSP00000415430.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.59
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs202151215; hg19: chr22-46704399;