rs2077750

Variant names:

• chr6-35122034-G-A
• rs2077750
• NM_001370687.1:c.578+83C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-0.96).
• 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 rank	MANE	Protein	UniProt
TCP11	NM_001370687.1	c.578+83C>T		intron_variant	Intron 5 of 9	ENST00000311875.11	NP_001357616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCP11	ENST00000311875.11	c.578+83C>T		intron_variant	Intron 5 of 9	1	NM_001370687.1	ENSP00000308708.6

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

African (AFR) AF: 0.0263 AC: 731 AN: 27778

American (AMR) AF: 0.189 AC: 8148 AN: 43180

Ashkenazi Jewish (ASJ) AF: 0.0541 AC: 1262 AN: 23346

East Asian (EAS) AF: 0.0155 AC: 593 AN: 38198

South Asian (SAS) AF: 0.0722 AC: 5611 AN: 77746

European-Finnish (FIN) AF: 0.190 AC: 9995 AN: 52496

Middle Eastern (MID) AF: 0.0263 AC: 135 AN: 5136

European-Non Finnish (NFE) AF: 0.194 AC: 167034 AN: 859294

Other (OTH) AF: 0.147 AC: 7479 AN: 50888

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

African (AFR) AF: 0.0332 AC: 1381 AN: 41536

American (AMR) AF: 0.148 AC: 2265 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0577 AC: 200 AN: 3468

East Asian (EAS) AF: 0.0166 AC: 86 AN: 5182

South Asian (SAS) AF: 0.0626 AC: 302 AN: 4828

European-Finnish (FIN) AF: 0.183 AC: 1932 AN: 10568

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12714 AN: 67960

Other (OTH) AF: 0.0849 AC: 179 AN: 2108

Alfa AF: 0.171 Hom.: 1354

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
PhyloP100		-0.0040
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: rs2077750; hg19: chr6-35089811;