NM_005730.4:c.535C>G

Variant names:

• chr12-57824059-G-C
• NM_005730.4:c.535C>G

Variant summary

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

The NM_005730.4(CTDSP2):​c.535C>G​(p.Arg179Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CTDSP2 NM_005730.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82

Genes affected

CTDSP2 (HGNC:17077): (CTD small phosphatase 2) Enables RNA polymerase II CTD heptapeptide repeat phosphatase activity. Involved in protein dephosphorylation. Predicted to be located in nucleoplasm. [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=0.27088553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTDSP2	NM_005730.4	c.535C>G	p.Arg179Gly	missense_variant	Exon 7 of 8	ENST00000398073.7	NP_005721.3
CTDSP2	XM_005268556.3	c.553C>G	p.Arg185Gly	missense_variant	Exon 7 of 8		XP_005268613.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTDSP2	ENST00000398073.7	c.535C>G	p.Arg179Gly	missense_variant	Exon 7 of 8	1	NM_005730.4	ENSP00000381148.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461758 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727162

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.19	T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;.
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Benign	0.10
Sift	Benign	0.10	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.17	B;.
Vest4		0.40
MutPred		0.49		Loss of solvent accessibility (P = 0.0159);.;
MVP		0.32
MPC		1.1
ClinPred		0.89	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.73
gMVP		0.62

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: chr12-58217842;