NM_001370687.1:c.457G>T

Variant names:

• chr6-35122238-C-A
• rs375000730
• NM_001370687.1:c.457G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001370687.1(TCP11):​c.457G>T​(p.Ala153Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: TCP11 NM_001370687.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.56
• Publications: 3 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.31050712).

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.457G>T	p.Ala153Ser	missense	Exon 5 of 10	NP_001357616.1	Q8WWU5-1
	TCP11	NM_001261817.2		c.442G>T	p.Ala148Ser	missense	Exon 5 of 10	NP_001248746.2	A0A6E1WXZ9
	TCP11	NM_001261818.2		c.358G>T	p.Ala120Ser	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.457G>T	p.Ala153Ser	missense	Exon 5 of 10	ENSP00000308708.6	Q8WWU5-1
	TCP11	ENST00000512012.5	TSL:1	c.457G>T	p.Ala153Ser	missense	Exon 4 of 9	ENSP00000425995.1	Q8WWU5-1
	TCP11	ENST00000244645.7	TSL:1	c.271G>T	p.Ala91Ser	missense	Exon 5 of 10	ENSP00000244645.3	Q8WWU5-2

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152146 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000557 AC: 14 AN: 251482 AF XY: 0.0000441

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000967

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000126 AC: 184 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.000120 AC XY: 87 AN XY: 727248

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

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: 0.0000116 AC: 1 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: 0.000162 AC: 180 AN: 1112010

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152146 Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4 AN XY: 74332

African (AFR) AF: 0.0000724 AC: 3 AN: 41420

American (AMR) AF: 0.0000655 AC: 1 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000575 Hom.: 0

Bravo AF: 0.000102

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

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	0.084
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.6
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.12
Sift	Uncertain	0.010	D
Sift4G	Benign	0.061	T
Polyphen		0.0070	B
Vest4		0.047
MVP		0.13
MPC		0.25
ClinPred		0.14	T
GERP RS		1.5
Varity_R		0.098
gMVP		0.088
Mutation Taster		=96/4	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: rs375000730; hg19: chr6-35090015;