rs140054

Variant names:

• chr22-46326503-T-C
• rs140054
• NM_016426.7:c.1573T>C

Your query was ambiguous. Multiple possible variants found:

• chr22-46326503-T-C
• chr22-46326503-T-G

Variant summary

Our verdict is Benign. The variant received -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. 14/19 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
• Publications: 29 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 -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTSE1	NM_016426.7	MANE Select	c.1573T>C	p.Trp525Arg	missense	Exon 9 of 12	NP_057510.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTSE1	ENST00000454366.2	TSL:1 MANE Select	c.1573T>C	p.Trp525Arg	missense	Exon 9 of 12	ENSP00000415430.1
	GTSE1	ENST00000466510.5	TSL:1	n.517T>C		non_coding_transcript_exon	Exon 3 of 3
	GTSE1	ENST00000479645.1	TSL:1	n.517T>C		non_coding_transcript_exon	Exon 3 of 4

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

GnomAD2 exomes AF: 0.945 AC: 237115 AN: 251018 AF XY: 0.944

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 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

African (AFR) AF: 0.988 AC: 33064 AN: 33480

American (AMR) AF: 0.956 AC: 42741 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.899 AC: 23481 AN: 26120

East Asian (EAS) AF: 1.00 AC: 39694 AN: 39698

South Asian (SAS) AF: 0.985 AC: 84904 AN: 86228

European-Finnish (FIN) AF: 0.939 AC: 50148 AN: 53392

Middle Eastern (MID) AF: 0.906 AC: 5225 AN: 5768

European-Non Finnish (NFE) AF: 0.922 AC: 1024803 AN: 1111822

Other (OTH) AF: 0.930 AC: 56175 AN: 60396

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

African (AFR) AF: 0.984 AC: 40938 AN: 41594

American (AMR) AF: 0.942 AC: 14421 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.900 AC: 3123 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5182 AN: 5182

South Asian (SAS) AF: 0.984 AC: 4757 AN: 4834

European-Finnish (FIN) AF: 0.944 AC: 10022 AN: 10622

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.925 AC: 62946 AN: 68042

Other (OTH) AF: 0.934 AC: 1977 AN: 2116

Alfa AF: 0.934 Hom.: 47198

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
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
PhyloP100		-0.34
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
Mutation Taster		=100/0	polymorphism (auto)

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