rs2395609

Variant names:

• chr6-35126373-G-C
• rs2395609
• NM_001370687.1:c.357+2689C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-35126373-G-C
• chr6-35126373-G-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.357+2689C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 151,934 control chromosomes in the GnomAD database, including 34,623 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 0.67 (34623 hom., cov: 30)
• Consequence: TCP11 NM_001370687.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.363
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370687.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCP11	NM_001370687.1	MANE Select	c.357+2689C>G		intron	N/A	NP_001357616.1
	TCP11	NM_001261817.2		c.342+2689C>G		intron	N/A	NP_001248746.2
	TCP11	NM_001261818.2		c.258+2689C>G		intron	N/A	NP_001248747.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCP11	ENST00000311875.11	TSL:1 MANE Select	c.357+2689C>G		intron	N/A	ENSP00000308708.6
	TCP11	ENST00000512012.5	TSL:1	c.357+2689C>G		intron	N/A	ENSP00000425995.1
	TCP11	ENST00000244645.7	TSL:1	c.171+2689C>G		intron	N/A	ENSP00000244645.3

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102260 AN: 151816 Hom.: 34603 Cov.: 30

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.801

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.724

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.673 AC: 102317 AN: 151934 Hom.: 34623 Cov.: 30 AF XY: 0.674 AC XY: 50029 AN XY: 74260

African (AFR) AF: 0.636 AC: 26328 AN: 41398

American (AMR) AF: 0.691 AC: 10541 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2854 AN: 3472

East Asian (EAS) AF: 0.619 AC: 3194 AN: 5164

South Asian (SAS) AF: 0.668 AC: 3218 AN: 4816

European-Finnish (FIN) AF: 0.676 AC: 7126 AN: 10542

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46573 AN: 67968

Other (OTH) AF: 0.716 AC: 1507 AN: 2106

Alfa AF: 0.667 Hom.: 3995

Bravo AF: 0.675

Asia WGS AF: 0.646 AC: 2244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.9
DANN	Benign	0.83
PhyloP100		-0.36
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: rs2395609; hg19: chr6-35094150;