6-35120526-G-T

Position:

• chr6-35120526-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001370687.1(TCP11):​c.836C>A​(p.Ala279Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TCP11 NM_001370687.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.38

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]

TCP11 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059154063).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCP11	NM_001370687.1	c.836C>A	p.Ala279Glu	missense_variant	7/10	ENST00000311875.11	NP_001357616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCP11	ENST00000311875.11	c.836C>A	p.Ala279Glu	missense_variant	7/10	1	NM_001370687.1	ENSP00000308708.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 05, 2024

The c.875C>A (p.A292E) alteration is located in exon 7 (coding exon 7) of the TCP11 gene. This alteration results from a C to A substitution at nucleotide position 875, causing the alanine (A) at amino acid position 292 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	0.10
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.8
DANN	Benign	0.40
DEOGEN2	Benign	0.0024	.;.;.;.;.;.;.;T;.;.
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.54	T;.;T;T;T;T;T;T;.;T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.059	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.6	.;.;.;.;.;.;.;L;.;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.5	N;N;N;N;.;N;N;N;N;N
REVEL	Benign	0.071
Sift	Benign	0.33	T;T;T;T;.;T;T;T;T;T
Sift4G	Benign	0.37	T;T;T;T;T;T;T;T;T;.
Polyphen		0.0030, 0.034	.;B;.;.;.;B;.;B;.;.
Vest4		0.18
MutPred		0.28		.;.;.;.;.;.;.;Loss of glycosylation at S275 (P = 0.1259);.;.;
MVP		0.088
MPC		0.17
ClinPred		0.089	T
GERP RS		3.1
Varity_R		0.069
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr6-35088303;