6-35120241-C-G

Variant names:

• chr6-35120241-C-G
• rs2234046
• NM_001370687.1:c.1033G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001370687.1(TCP11):​c.1033G>C​(p.Gly345Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000158 in 1,614,192 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts 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. G345S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00051 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: TCP11 NM_001370687.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08
• Publications: 4 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011357665).

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.1033G>C	p.Gly345Arg	missense	Exon 8 of 10	NP_001357616.1	Q8WWU5-1
	TCP11	NM_001261817.2		c.1018G>C	p.Gly340Arg	missense	Exon 8 of 10	NP_001248746.2	A0A6E1WXZ9
	TCP11	NM_001261818.2		c.934G>C	p.Gly312Arg	missense	Exon 7 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.1033G>C	p.Gly345Arg	missense	Exon 8 of 10	ENSP00000308708.6	Q8WWU5-1
	TCP11	ENST00000512012.5	TSL:1	c.1033G>C	p.Gly345Arg	missense	Exon 7 of 9	ENSP00000425995.1	Q8WWU5-1
	TCP11	ENST00000244645.7	TSL:1	c.847G>C	p.Gly283Arg	missense	Exon 8 of 10	ENSP00000244645.3	Q8WWU5-2

Frequencies

GnomAD3 genomes AF: 0.000506 AC: 77 AN: 152186 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000334 AC: 84 AN: 251372 AF XY: 0.000302

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00156

Gnomad ASJ exome AF: 0.00119

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000968

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000122 AC: 178 AN: 1461888 Hom.: 0 Cov.: 30 AF XY: 0.000109 AC XY: 79 AN XY: 727242

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00170 AC: 76 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00142 AC: 37 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

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: 0.0000216 AC: 24 AN: 1112008

Other (OTH) AF: 0.000662 AC: 40 AN: 60396

GnomAD4 genome AF: 0.000506 AC: 77 AN: 152304 Hom.: 1 Cov.: 32 AF XY: 0.000457 AC XY: 34 AN XY: 74474

African (AFR) AF: 0.0000963 AC: 4 AN: 41556

American (AMR) AF: 0.00386 AC: 59 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68034

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.000272 Hom.: 0

Bravo AF: 0.000873

ExAC AF: 0.000239 AC: 29

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.056	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.011	T
MetaSVM	Uncertain	-0.039	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		4.1
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.23
MVP		0.31
MPC		0.62
ClinPred		0.26	T
GERP RS		5.0
Varity_R		0.64
gMVP		0.65
Mutation Taster		=77/23	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: rs2234046; hg19: chr6-35088018;