rs3756856

Positions:

• chr6-35142928-A-G

Variant summary

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

The ENST00000418521.6(TCP11):​c.-66+5496T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,154 control chromosomes in the GnomAD database, including 1,939 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 0.15 (1939 hom., cov: 32)
• Consequence: TCP11 ENST00000418521.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.824

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCP11	ENST00000418521.6	c.-66+5496T>C		intron_variant		5		ENSP00000415320

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22632 AN: 152038 Hom.: 1936 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.0970

Gnomad SAS AF: 0.0790

Gnomad FIN AF: 0.0619

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.149 AC: 22640 AN: 152154 Hom.: 1939 Cov.: 32 AF XY: 0.144 AC XY: 10694 AN XY: 74374

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.0972

Gnomad4 SAS AF: 0.0795

Gnomad4 FIN AF: 0.0619

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.180

Alfa AF: 0.150 Hom.: 2357

Bravo AF: 0.159

Asia WGS AF: 0.102 AC: 358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.94
DANN	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3756856; hg19: chr6-35110705;