rs2077750

Positions:

• chr6-35122034-G-A

Variant summary

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

The NM_001370687.1(TCP11):​c.578+83C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 1,330,192 control chromosomes in the GnomAD database, including 21,011 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 0.13 (1660 hom., cov: 31)
  • Exomes 𝑓: 0.17 (19351 hom.)
• Consequence: TCP11 NM_001370687.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) 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
TCP11	NM_001370687.1	c.578+83C>T		intron_variant		ENST00000311875.11	NP_001357616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCP11	ENST00000311875.11	c.578+83C>T		intron_variant		1	NM_001370687.1	ENSP00000308708	P3

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19195 AN: 152012 Hom.: 1658 Cov.: 31

Gnomad AFR AF: 0.0333

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.0577

Gnomad EAS AF: 0.0162

Gnomad SAS AF: 0.0619

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.0858

GnomAD4 exome AF: 0.171 AC: 200988 AN: 1178062 Hom.: 19351 AF XY: 0.166 AC XY: 98822 AN XY: 596550

Gnomad4 AFR exome AF: 0.0263

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.0541

Gnomad4 EAS exome AF: 0.0155

Gnomad4 SAS exome AF: 0.0722

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.194

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.126 AC: 19199 AN: 152130 Hom.: 1660 Cov.: 31 AF XY: 0.123 AC XY: 9162 AN XY: 74400

Gnomad4 AFR AF: 0.0332

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.0577

Gnomad4 EAS AF: 0.0166

Gnomad4 SAS AF: 0.0626

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.0849

Alfa AF: 0.166 Hom.: 802

Bravo AF: 0.120

Asia WGS AF: 0.0460 AC: 162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.4
DANN	Benign	0.64

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: rs2077750; hg19: chr6-35089811;