rs140054

Positions:

• chr22-46326503-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016426.7(GTSE1):​c.1573T>C​(p.Trp525Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.932 in 1,613,986 control chromosomes in the GnomAD database, including 701,943 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 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: 𝑓 0.95 (68572 hom., cov: 37)
  • Exomes 𝑓: 0.93 (633371 hom.)
• Consequence: GTSE1 NM_016426.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1933122E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTSE1	NM_016426.7	c.1573T>C	p.Trp525Arg	missense_variant	9/12	ENST00000454366.2	NP_057510.5
GTSE1	XM_047441391.1	c.1573T>C	p.Trp525Arg	missense_variant	8/11		XP_047297347.1
GTSE1	XM_047441392.1	c.1573T>C	p.Trp525Arg	missense_variant	9/10		XP_047297348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTSE1	ENST00000454366.2	c.1573T>C	p.Trp525Arg	missense_variant	9/12	1	NM_016426.7	ENSP00000415430	P1
GTSE1	ENST00000466510.5	n.517T>C		non_coding_transcript_exon_variant	3/3	1
GTSE1	ENST00000479645.1	n.517T>C		non_coding_transcript_exon_variant	3/4	1

Frequencies

GnomAD3 genomes AF: 0.948 AC: 144372 AN: 152258 Hom.: 68512 Cov.: 37

Gnomad AFR AF: 0.984

Gnomad AMI AF: 0.944

Gnomad AMR AF: 0.942

Gnomad ASJ AF: 0.900

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.984

Gnomad FIN AF: 0.944

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.925

Gnomad OTH AF: 0.934

GnomAD3 exomes AF: 0.945 AC: 237115 AN: 251018 Hom.: 112113 AF XY: 0.944 AC XY: 128127 AN XY: 135732

Gnomad AFR exome AF: 0.987

Gnomad AMR exome AF: 0.958

Gnomad ASJ exome AF: 0.899

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.985

Gnomad FIN exome AF: 0.939

Gnomad NFE exome AF: 0.920

Gnomad OTH exome AF: 0.925

GnomAD4 exome AF: 0.931 AC: 1360235 AN: 1461610 Hom.: 633371 Cov.: 55 AF XY: 0.932 AC XY: 677533 AN XY: 727092

Gnomad4 AFR exome AF: 0.988

Gnomad4 AMR exome AF: 0.956

Gnomad4 ASJ exome AF: 0.899

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.985

Gnomad4 FIN exome AF: 0.939

Gnomad4 NFE exome AF: 0.922

Gnomad4 OTH exome AF: 0.930

GnomAD4 genome AF: 0.948 AC: 144492 AN: 152376 Hom.: 68572 Cov.: 37 AF XY: 0.950 AC XY: 70795 AN XY: 74510

Gnomad4 AFR AF: 0.984

Gnomad4 AMR AF: 0.942

Gnomad4 ASJ AF: 0.900

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.984

Gnomad4 FIN AF: 0.944

Gnomad4 NFE AF: 0.925

Gnomad4 OTH AF: 0.934

Alfa AF: 0.931 Hom.: 35957

Bravo AF: 0.948

TwinsUK AF: 0.922 AC: 3420

ALSPAC AF: 0.917 AC: 3536

ESP6500AA AF: 0.983 AC: 4332

ESP6500EA AF: 0.919 AC: 7900

ExAC AF: 0.944 AC: 114550

Asia WGS AF: 0.991 AC: 3448 AN: 3478

EpiCase AF: 0.919

EpiControl AF: 0.917

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.11
DANN	Benign	0.31
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0093	N
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.37	T
PROVEAN	Benign	3.8	N
REVEL	Benign	0.013
Sift	Benign	1.0	T
Sift4G	Benign	0.85	T
Vest4		0.013
MPC		0.26
ClinPred		0.012	T
GERP RS		-3.8
gMVP		0.12

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: rs140054; hg19: chr22-46722400; COSMIC: COSV71888982; COSMIC: COSV71888982;