6-35118499-G-C

Variant names:

• chr6-35118499-G-C
• NM_001370687.1:c.1282C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001366330.2(TCP11):​c.878C>G​(p.Ser293*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TCP11 NM_001366330.2 stop_gained
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.86

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCP11	NM_001370687.1	c.1282C>G	p.Gln428Glu	missense_variant, splice_region_variant	Exon 10 of 10	ENST00000311875.11	NP_001357616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCP11	ENST00000311875.11	c.1282C>G	p.Gln428Glu	missense_variant, splice_region_variant	Exon 10 of 10	1	NM_001370687.1	ENSP00000308708.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 15, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1321C>G (p.Q441E) alteration is located in exon 10 (coding exon 10) of the TCP11 gene. This alteration results from a C to G substitution at nucleotide position 1321, causing the glutamine (Q) at amino acid position 441 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.0021	.;.;.;.;.;.;.;T;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.91	D;.;D;D;D;D;D;D;.
M_CAP	Benign	0.0053	T
MetaRNN	Uncertain	0.51	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	.;.;.;.;.;.;.;M;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.5	N;N;N;N;.;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.18	T;T;T;T;.;T;T;T;T
Sift4G	Benign	0.16	T;T;T;T;T;T;T;T;T
Polyphen		0.38, 0.94	.;B;.;.;.;B;.;P;.
Vest4		0.16
MutPred		0.83		.;.;.;.;.;.;.;Loss of MoRF binding (P = 0.3422);.;
MVP		0.44
MPC		0.35
ClinPred		0.81	D
GERP RS		4.5
Varity_R		0.23
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-35086276;