ENST00000418521.6:c.-66+5496T>C

Variant names:

• chr6-35142928-A-G
• rs3756856
• ENST00000418521.6:c.-66+5496T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCP11	ENST00000418521.6	c.-66+5496T>C		intron_variant	Intron 1 of 8	5		ENSP00000415320.2

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

African (AFR) AF: 0.187 AC: 7773 AN: 41480

American (AMR) AF: 0.132 AC: 2026 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1063 AN: 3470

East Asian (EAS) AF: 0.0972 AC: 504 AN: 5186

South Asian (SAS) AF: 0.0795 AC: 384 AN: 4830

European-Finnish (FIN) AF: 0.0619 AC: 655 AN: 10588

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9739 AN: 67992

Other (OTH) AF: 0.180 AC: 379 AN: 2108

Alfa AF: 0.151 Hom.: 3320

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
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3756856; hg19: chr6-35110705;