6-35122320-T-C

Variant names:

• chr6-35122320-T-C
• rs2234044
• NM_001370687.1:c.375A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001370687.1(TCP11):​c.375A>G​(p.Leu125Leu) 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
• Publications: 22 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 -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 rank	MANE	Protein	UniProt
TCP11	NM_001370687.1	c.375A>G	p.Leu125Leu	synonymous_variant	Exon 5 of 10	ENST00000311875.11	NP_001357616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCP11	ENST00000311875.11	c.375A>G	p.Leu125Leu	synonymous_variant	Exon 5 of 10	1	NM_001370687.1	ENSP00000308708.6

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

GnomAD2 exomes AF: 0.136 AC: 34240 AN: 251252 AF XY: 0.135

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 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

African (AFR) AF: 0.295 AC: 9882 AN: 33476

American (AMR) AF: 0.106 AC: 4725 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 8013 AN: 26136

East Asian (EAS) AF: 0.0763 AC: 3029 AN: 39698

South Asian (SAS) AF: 0.0823 AC: 7101 AN: 86254

European-Finnish (FIN) AF: 0.0616 AC: 3293 AN: 53418

Middle Eastern (MID) AF: 0.185 AC: 1067 AN: 5764

European-Non Finnish (NFE) AF: 0.154 AC: 171436 AN: 1111914

Other (OTH) AF: 0.166 AC: 10001 AN: 60386

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

African (AFR) AF: 0.292 AC: 12095 AN: 41450

American (AMR) AF: 0.148 AC: 2264 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1069 AN: 3468

East Asian (EAS) AF: 0.0965 AC: 500 AN: 5180

South Asian (SAS) AF: 0.0817 AC: 394 AN: 4824

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

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9814 AN: 67990

Other (OTH) AF: 0.201 AC: 424 AN: 2108

Alfa AF: 0.158 Hom.: 5852

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
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2234044; hg19: chr6-35090097;