3-37963170-A-G

Position:

• chr3-37963170-A-G

Variant summary

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

The NM_001008392.2(CTDSPL):​c.268-1401A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,114 control chromosomes in the GnomAD database, including 3,933 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 0.21 (3933 hom., cov: 32)
• Consequence: CTDSPL NM_001008392.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTDSPL	NM_001008392.2	c.268-1401A>G		intron_variant		ENST00000273179.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTDSPL	ENST00000273179.10	c.268-1401A>G		intron_variant		1	NM_001008392.2	P4

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31270 AN: 151996 Hom.: 3918 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0520

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.186

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.206 AC: 31329 AN: 152114 Hom.: 3933 Cov.: 32 AF XY: 0.202 AC XY: 15007 AN XY: 74356

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.0521

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.184

Alfa AF: 0.175 Hom.: 2596

Bravo AF: 0.213

Asia WGS AF: 0.163 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.48
DANN	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6776745; hg19: chr3-38004661;