6-35122123-A-T

Variant names:

• chr6-35122123-A-T
• rs778500766
• NM_001370687.1:c.572T>A

Variant summary

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

The NM_001370687.1(TCP11):​c.572T>A​(p.Leu191Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L191P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TCP11 NM_001370687.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.48
• 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 2 ACMG points.

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

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.572T>A	p.Leu191Gln	missense	Exon 5 of 10	NP_001357616.1	Q8WWU5-1
	TCP11	NM_001261817.2		c.557T>A	p.Leu186Gln	missense	Exon 5 of 10	NP_001248746.2	A0A6E1WXZ9
	TCP11	NM_001261818.2		c.473T>A	p.Leu158Gln	missense	Exon 4 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.572T>A	p.Leu191Gln	missense	Exon 5 of 10	ENSP00000308708.6	Q8WWU5-1
	TCP11	ENST00000512012.5	TSL:1	c.572T>A	p.Leu191Gln	missense	Exon 4 of 9	ENSP00000425995.1	Q8WWU5-1
	TCP11	ENST00000244645.7	TSL:1	c.386T>A	p.Leu129Gln	missense	Exon 5 of 10	ENSP00000244645.3	Q8WWU5-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33478

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

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 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: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Uncertain	0.36
Eigen_PC	Benign	0.19
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		8.5
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.56		Gain of MoRF binding (P = 0.0848)
MVP		0.37
MPC		0.61
ClinPred		0.98	D
GERP RS		4.2
Varity_R		0.87
gMVP		0.43
Mutation Taster		=90/10	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: rs778500766; hg19: chr6-35089900;