NM_001008392.2:c.426+1335T>C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

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 = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTDSPL	NM_001008392.2	c.426+1335T>C		intron_variant	Intron 5 of 7	ENST00000273179.10	NP_001008393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTDSPL	ENST00000273179.10	c.426+1335T>C		intron_variant	Intron 5 of 7	1	NM_001008392.2	ENSP00000273179.5

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

Gnomad4 AFR AF: 0.939

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.852

Gnomad4 FIN AF: 0.661

Gnomad4 NFE AF: 0.717

Gnomad4 OTH AF: 0.759

Alfa AF: 0.726 Hom.: 54116

Bravo AF: 0.776

Asia WGS AF: 0.838 AC: 2913 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	1.6
DANN	Benign	0.63

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: rs7372209; hg19: chr3-38010708;