rs2395609

Positions:

• chr6-35126373-G-C
• chr6-35126373-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370687.1(TCP11):​c.357+2689C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 151,934 control chromosomes in the GnomAD database, including 34,623 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 0.67 (34623 hom., cov: 30)
• Consequence: TCP11 NM_001370687.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.363

Genes affected

TCP11 (HGNC:11658): (t-complex 11) Predicted to be involved in several processes, including protein kinase A signaling; regulation of cAMP-mediated signaling; and regulation of sperm capacitation. Located in acrosomal vesicle and sperm flagellum. [provided by Alliance of Genome Resources, Apr 2022]

TCP11 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCP11	NM_001370687.1	c.357+2689C>G		intron_variant		ENST00000311875.11	NP_001357616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCP11	ENST00000311875.11	c.357+2689C>G		intron_variant		1	NM_001370687.1	ENSP00000308708.6

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102260 AN: 151816 Hom.: 34603 Cov.: 30

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.801

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.673 AC: 102317 AN: 151934 Hom.: 34623 Cov.: 30 AF XY: 0.674 AC XY: 50029 AN XY: 74260

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.822

Gnomad4 EAS AF: 0.619

Gnomad4 SAS AF: 0.668

Gnomad4 FIN AF: 0.676

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.716

Alfa AF: 0.667 Hom.: 3995

Bravo AF: 0.675

Asia WGS AF: 0.646 AC: 2244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.9
DANN	Benign	0.83

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

LitVar

Other links and lift over

dbSNP: rs2395609; hg19: chr6-35094150;