3-37980821-G-T

Variant names:

• chr3-37980821-G-T
• rs756522638
• NM_001008392.2:c.785G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001008392.2(CTDSPL):​c.785G>T​(p.Arg262Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R262W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTDSPL NM_001008392.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45
• Publications: 2 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24759623).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTDSPL	NM_001008392.2	MANE Select	c.785G>T	p.Arg262Leu	missense	Exon 8 of 8	NP_001008393.1	O15194-1
	CTDSPL	NM_001438028.1		c.785G>T	p.Arg262Leu	missense	Exon 8 of 9	NP_001424957.1	H7C353
	CTDSPL	NM_001438653.1		c.752G>T	p.Arg251Leu	missense	Exon 7 of 8	NP_001425582.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTDSPL	ENST00000273179.10	TSL:1 MANE Select	c.785G>T	p.Arg262Leu	missense	Exon 8 of 8	ENSP00000273179.5	O15194-1
	CTDSPL	ENST00000443503.6	TSL:1	c.752G>T	p.Arg251Leu	missense	Exon 7 of 7	ENSP00000398288.2	O15194-2
	CTDSPL	ENST00000436654.2	TSL:3	c.785G>T	p.Arg262Leu	missense	Exon 8 of 9	ENSP00000409600.2	H7C353

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.085
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.47	N
PhyloP100		2.5
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.093
Sift	Benign	0.046	D
Sift4G	Benign	0.11	T
Polyphen		0.017	B
Vest4		0.37
MutPred		0.37		Gain of glycosylation at Y267 (P = 0.0031)
MVP		0.49
MPC		0.88
ClinPred		0.98	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.42
gMVP		0.48
Mutation Taster		=55/45	polymorphism

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

Other links and lift over

dbSNP: rs756522638; hg19: chr3-38022312;