6-35118319-T-C

Variant names:

• chr6-35118319-T-C
• rs765365117
• NM_001370687.1:c.1462A>G

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.1462A>G​(p.Thr488Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T488S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TCP11 NM_001370687.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• 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=0.11028972).

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.1462A>G	p.Thr488Ala	missense	Exon 10 of 10	NP_001357616.1	Q8WWU5-1
	TCP11	NM_001261817.2		c.1447A>G	p.Thr483Ala	missense	Exon 10 of 10	NP_001248746.2	A0A6E1WXZ9
	TCP11	NM_001261818.2		c.1363A>G	p.Thr455Ala	missense	Exon 9 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.1462A>G	p.Thr488Ala	missense	Exon 10 of 10	ENSP00000308708.6	Q8WWU5-1
	TCP11	ENST00000512012.5	TSL:1	c.1462A>G	p.Thr488Ala	missense	Exon 9 of 9	ENSP00000425995.1	Q8WWU5-1
	TCP11	ENST00000244645.7	TSL:1	c.1276A>G	p.Thr426Ala	missense	Exon 10 of 10	ENSP00000244645.3	Q8WWU5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.7
DANN	Benign	0.89
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.14	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.2
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.0080
Sift	Benign	0.044	D
Sift4G	Benign	0.23	T
Polyphen		0.019	B
Vest4		0.058
MutPred		0.40		Gain of ubiquitination at K487 (P = 0.102)
MVP		0.040
MPC		0.13
ClinPred		0.098	T
GERP RS		2.9
Varity_R		0.070
gMVP		0.081
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs765365117; hg19: chr6-35086096;