rs6776745

Variant names:

• chr3-37963170-A-G
• rs6776745
• NM_001008392.2:c.268-1401A>G

Variant summary

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

The NM_001008392.2(CTDSPL):​c.268-1401A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,114 control chromosomes in the GnomAD database, including 3,933 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 0.21 (3933 hom., cov: 32)
• Consequence: CTDSPL NM_001008392.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.343 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTDSPL	NM_001008392.2	MANE Select	c.268-1401A>G		intron	N/A	NP_001008393.1	O15194-1
	CTDSPL	NM_001438028.1		c.268-1401A>G		intron	N/A	NP_001424957.1	H7C353
	CTDSPL	NM_001438653.1		c.235-1401A>G		intron	N/A	NP_001425582.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTDSPL	ENST00000273179.10	TSL:1 MANE Select	c.268-1401A>G		intron	N/A	ENSP00000273179.5	O15194-1
	CTDSPL	ENST00000443503.6	TSL:1	c.235-1401A>G		intron	N/A	ENSP00000398288.2	O15194-2
	CTDSPL	ENST00000436654.2	TSL:3	c.268-1401A>G		intron	N/A	ENSP00000409600.2	H7C353

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31270 AN: 151996 Hom.: 3918 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0520

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.206 AC: 31329 AN: 152114 Hom.: 3933 Cov.: 32 AF XY: 0.202 AC XY: 15007 AN XY: 74356

African (AFR) AF: 0.347 AC: 14393 AN: 41446

American (AMR) AF: 0.131 AC: 2006 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 429 AN: 3472

East Asian (EAS) AF: 0.0521 AC: 270 AN: 5182

South Asian (SAS) AF: 0.233 AC: 1122 AN: 4824

European-Finnish (FIN) AF: 0.119 AC: 1260 AN: 10586

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11298 AN: 68002

Other (OTH) AF: 0.184 AC: 389 AN: 2114

Alfa AF: 0.176 Hom.: 3228

Bravo AF: 0.213

Asia WGS AF: 0.163 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.48
DANN	Benign	0.31
PhyloP100		-0.27
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: rs6776745; hg19: chr3-38004661;