3-37969217-T-C

Variant names:

• chr3-37969217-T-C
• rs7372209
• NM_001008392.2:c.426+1335T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001008392.2(CTDSPL):​c.426+1335T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 152,258 control chromosomes in the GnomAD database, including 46,255 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 0.77 (46255 hom., cov: 34)
• Consequence: CTDSPL NM_001008392.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.765
• Publications: 92 publications found

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]

MIR26A1 (HGNC:31610): (microRNA 26a-1) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -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 = 0.931 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008392.2. 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
	CTDSPL	NM_001008392.2	MANE Select	c.426+1335T>C		intron	N/A	NP_001008393.1
	CTDSPL	NM_001438028.1		c.426+1335T>C		intron	N/A	NP_001424957.1
	CTDSPL	NM_001438653.1		c.393+1335T>C		intron	N/A	NP_001425582.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTDSPL	ENST00000273179.10	TSL:1 MANE Select	c.426+1335T>C		intron	N/A	ENSP00000273179.5
	CTDSPL	ENST00000443503.6	TSL:1	c.393+1335T>C		intron	N/A	ENSP00000398288.2
	CTDSPL	ENST00000436654.2	TSL:3	c.426+1335T>C		intron	N/A	ENSP00000409600.2

Frequencies

GnomAD3 genomes AF: 0.770 AC: 117178 AN: 152140 Hom.: 46202 Cov.: 34

Gnomad AFR AF: 0.939

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.755

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

GnomAD4 genome AF: 0.770 AC: 117288 AN: 152258 Hom.: 46255 Cov.: 34 AF XY: 0.768 AC XY: 57156 AN XY: 74440

African (AFR) AF: 0.939 AC: 39037 AN: 41564

American (AMR) AF: 0.642 AC: 9815 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2231 AN: 3470

East Asian (EAS) AF: 0.719 AC: 3708 AN: 5158

South Asian (SAS) AF: 0.852 AC: 4114 AN: 4828

European-Finnish (FIN) AF: 0.661 AC: 7009 AN: 10600

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48771 AN: 68018

Other (OTH) AF: 0.759 AC: 1604 AN: 2114

Alfa AF: 0.735 Hom.: 125753

Bravo AF: 0.776

Asia WGS AF: 0.838 AC: 2913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.63
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7372209; hg19: chr3-38010708;