3-37947114-T-C

Variant names:

• chr3-37947114-T-C
• NM_001008392.2:c.137T>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001008392.2(CTDSPL):​c.137T>C​(p.Phe46Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTDSPL NM_001008392.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.52

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.393286).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTDSPL	NM_001008392.2	c.137T>C	p.Phe46Ser	missense_variant	Exon 2 of 8	ENST00000273179.10	NP_001008393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTDSPL	ENST00000273179.10	c.137T>C	p.Phe46Ser	missense_variant	Exon 2 of 8	1	NM_001008392.2	ENSP00000273179.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 02, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.137T>C (p.F46S) alteration is located in exon 2 (coding exon 2) of the CTDSPL gene. This alteration results from a T to C substitution at nucleotide position 137, causing the phenylalanine (F) at amino acid position 46 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	.;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.041	D;D
Polyphen		0.21	B;B
Vest4		0.61
MutPred		0.38		Gain of glycosylation at S41 (P = 0.0037);Gain of glycosylation at S41 (P = 0.0037);
MVP		0.30
MPC		1.5
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.80
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-37988605;