3-37954986-T-G

Position:

• chr3-37954986-T-G

Variant summary

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

The ENST00000273179.10(CTDSPL):​c.235-2125T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,188 control chromosomes in the GnomAD database, including 5,885 homozygotes. 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: 𝑓 0.24 (5885 hom., cov: 32)
  • Exomes 𝑓: 0.045 (0 hom.)
• Consequence: CTDSPL ENST00000273179.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510

Genes affected

CTDSPL (HGNC:16890): (CTD small phosphatase like) Predicted to enable RNA polymerase II CTD heptapeptide repeat phosphatase activity. Predicted to be involved in protein dephosphorylation. Predicted to act upstream of or within negative regulation of G1/S transition of mitotic cell cycle and negative regulation of protein phosphorylation. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTDSPL	NM_001008392.2	c.235-2125T>G		intron_variant		ENST00000273179.10	NP_001008393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTDSPL	ENST00000273179.10	c.235-2125T>G		intron_variant		1	NM_001008392.2	ENSP00000273179	P4

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36000 AN: 152048 Hom.: 5862 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.0530

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.219

GnomAD4 exome AF: 0.0455 AC: 1 AN: 22 Hom.: 0 Cov.: 0 AF XY: 0.0556 AC XY: 1 AN XY: 18

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0556

GnomAD4 genome AF: 0.237 AC: 36064 AN: 152166 Hom.: 5885 Cov.: 32 AF XY: 0.234 AC XY: 17379 AN XY: 74398

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.0531

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.216

Alfa AF: 0.185 Hom.: 1889

Bravo AF: 0.252

Asia WGS AF: 0.147 AC: 515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.1
DANN	Benign	0.32

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: rs9311171; hg19: chr3-37996477; COSMIC: COSV56200479;