22-46308531-G-C

Variant names:

• chr22-46308531-G-C
• NM_016426.7:c.350G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016426.7(GTSE1):​c.350G>C​(p.Arg117Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GTSE1 NM_016426.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14247948).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTSE1	NM_016426.7	c.350G>C	p.Arg117Pro	missense_variant	Exon 4 of 12	ENST00000454366.2	NP_057510.5
GTSE1	XM_047441391.1	c.350G>C	p.Arg117Pro	missense_variant	Exon 3 of 11		XP_047297347.1
GTSE1	XM_047441392.1	c.350G>C	p.Arg117Pro	missense_variant	Exon 4 of 10		XP_047297348.1
GTSE1	XR_007067974.1	n.433G>C		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.350G>C	p.Arg117Pro	missense_variant	Exon 4 of 12	1	NM_016426.7	ENSP00000415430.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461830 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727214

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Uncertain	0.99
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.18	N
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.065
Sift	Benign	0.040	D
Sift4G	Benign	0.11	T
Vest4		0.17
MVP		0.16
MPC		0.73
ClinPred		0.96	D
GERP RS		-2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-46704428;