rs756781573

Variant names:

• chr6-35120183-G-A
• rs756781573
• NM_001370687.1:c.1091C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-35120183-G-A
• chr6-35120183-G-C
• chr6-35120183-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001370687.1(TCP11):​c.1091C>T​(p.Ser364Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: TCP11 NM_001370687.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19809103).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCP11	NM_001370687.1	c.1091C>T	p.Ser364Phe	missense_variant	Exon 8 of 10	ENST00000311875.11	NP_001357616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCP11	ENST00000311875.11	c.1091C>T	p.Ser364Phe	missense_variant	Exon 8 of 10	1	NM_001370687.1	ENSP00000308708.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251224 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135770

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000205 AC: 30 AN: 1461834 Hom.: 0 Cov.: 30 AF XY: 0.0000206 AC XY: 15 AN XY: 727210

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000264

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0047	.;.;.;.;.;.;.;T;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.63	T;.;T;T;T;T;T;T;.
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.20	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	.;.;.;.;.;.;.;M;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.5	N;N;N;N;.;N;N;N;N
REVEL	Benign	0.050
Sift	Uncertain	0.020	D;D;D;D;.;D;D;D;D
Sift4G	Uncertain	0.012	D;D;D;D;D;D;D;D;D
Polyphen		0.18, 0.84	.;B;.;.;.;B;.;P;.
Vest4		0.20
MutPred		0.56		.;.;.;.;.;.;.;Loss of disorder (P = 0.0106);.;
MVP		0.39
MPC		0.41
ClinPred		0.34	T
GERP RS		1.7
Varity_R		0.056
gMVP		0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs756781573; hg19: chr6-35087960;