rs2234044

Positions:

• chr6-35122320-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001370687.1(TCP11):​c.375A>G​(p.Leu125=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,613,856 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 0.18 (3067 hom., cov: 31)
  • Exomes 𝑓: 0.15 (17944 hom.)
• Consequence: TCP11 NM_001370687.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-1.1 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCP11	NM_001370687.1	c.375A>G	p.Leu125=	synonymous_variant	5/10	ENST00000311875.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCP11	ENST00000311875.11	c.375A>G	p.Leu125=	synonymous_variant	5/10	1	NM_001370687.1	P3

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27306 AN: 151972 Hom.: 3061 Cov.: 31

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.0963

Gnomad SAS AF: 0.0812

Gnomad FIN AF: 0.0619

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.202

GnomAD3 exomes AF: 0.136 AC: 34240 AN: 251252 Hom.: 2935 AF XY: 0.135 AC XY: 18339 AN XY: 135810

Gnomad AFR exome AF: 0.293

Gnomad AMR exome AF: 0.100

Gnomad ASJ exome AF: 0.308

Gnomad EAS exome AF: 0.0976

Gnomad SAS exome AF: 0.0807

Gnomad FIN exome AF: 0.0616

Gnomad NFE exome AF: 0.144

Gnomad OTH exome AF: 0.157

GnomAD4 exome AF: 0.150 AC: 218547 AN: 1461766 Hom.: 17944 Cov.: 32 AF XY: 0.148 AC XY: 107309 AN XY: 727184

Gnomad4 AFR exome AF: 0.295

Gnomad4 AMR exome AF: 0.106

Gnomad4 ASJ exome AF: 0.307

Gnomad4 EAS exome AF: 0.0763

Gnomad4 SAS exome AF: 0.0823

Gnomad4 FIN exome AF: 0.0616

Gnomad4 NFE exome AF: 0.154

Gnomad4 OTH exome AF: 0.166

GnomAD4 genome AF: 0.180 AC: 27339 AN: 152090 Hom.: 3067 Cov.: 31 AF XY: 0.174 AC XY: 12940 AN XY: 74346

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.0965

Gnomad4 SAS AF: 0.0817

Gnomad4 FIN AF: 0.0619

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.201

Alfa AF: 0.158 Hom.: 4459

Bravo AF: 0.194

Asia WGS AF: 0.107 AC: 373 AN: 3478

EpiCase AF: 0.155

EpiControl AF: 0.158

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.2
DANN	Benign	0.70

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: rs2234044; hg19: chr6-35090097;