6-35120508-G-A

Variant names:

• chr6-35120508-G-A
• rs376470025
• NM_001370687.1:c.854C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001370687.1(TCP11):​c.854C>T​(p.Pro285Leu) 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. 15/22 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: 1.15
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1028972).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCP11	NM_001370687.1	MANE Select	c.854C>T	p.Pro285Leu	missense	Exon 7 of 10	NP_001357616.1	Q8WWU5-1
	TCP11	NM_001261817.2		c.839C>T	p.Pro280Leu	missense	Exon 7 of 10	NP_001248746.2	A0A6E1WXZ9
	TCP11	NM_001261818.2		c.755C>T	p.Pro252Leu	missense	Exon 6 of 9	NP_001248747.1	Q8WWU5-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCP11	ENST00000311875.11	TSL:1 MANE Select	c.854C>T	p.Pro285Leu	missense	Exon 7 of 10	ENSP00000308708.6	Q8WWU5-1
	TCP11	ENST00000512012.5	TSL:1	c.854C>T	p.Pro285Leu	missense	Exon 6 of 9	ENSP00000425995.1	Q8WWU5-1
	TCP11	ENST00000244645.7	TSL:1	c.668C>T	p.Pro223Leu	missense	Exon 7 of 10	ENSP00000244645.3	Q8WWU5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.84
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.2
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.060
Sift	Benign	0.12	T
Sift4G	Benign	0.84	T
Polyphen		0.0040	B
Vest4		0.16
MutPred		0.35		Loss of glycosylation at P285 (P = 0.0102)
MVP		0.18
MPC		0.15
ClinPred		0.14	T
GERP RS		4.1
Varity_R		0.079
gMVP		0.44
Mutation Taster		=95/5	polymorphism

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: rs376470025; hg19: chr6-35088285;