rs12750774

Positions:

• chr1-154544001-G-A
• chr1-154544001-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000368482.8(TDRD10):​c.542G>A​(p.Arg181Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 1,613,918 control chromosomes in the GnomAD database, including 66,805 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.21 (4564 hom., cov: 32)
  • Exomes 𝑓: 0.28 (62241 hom.)
• Consequence: TDRD10 ENST00000368482.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462

Genes affected

TDRD10 (HGNC:25316): (tudor domain containing 10) Predicted to enable RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004920125).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRD10	NM_182499.4	c.542G>A	p.Arg181Gln	missense_variant	9/13	ENST00000368482.8	NP_872305.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRD10	ENST00000368482.8	c.542G>A	p.Arg181Gln	missense_variant	9/13	1	NM_182499.4	ENSP00000357467	P1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32708 AN: 152034 Hom.: 4566 Cov.: 32

Gnomad AFR AF: 0.0553

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.0285

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.230

GnomAD3 exomes AF: 0.236 AC: 59225 AN: 251394 Hom.: 8289 AF XY: 0.238 AC XY: 32327 AN XY: 135876

Gnomad AFR exome AF: 0.0486

Gnomad AMR exome AF: 0.246

Gnomad ASJ exome AF: 0.244

Gnomad EAS exome AF: 0.0210

Gnomad SAS exome AF: 0.143

Gnomad FIN exome AF: 0.297

Gnomad NFE exome AF: 0.305

Gnomad OTH exome AF: 0.268

GnomAD4 exome AF: 0.282 AC: 412325 AN: 1461766 Hom.: 62241 Cov.: 46 AF XY: 0.279 AC XY: 202793 AN XY: 727190

Gnomad4 AFR exome AF: 0.0467

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.249

Gnomad4 EAS exome AF: 0.0411

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.289

Gnomad4 NFE exome AF: 0.312

Gnomad4 OTH exome AF: 0.251

GnomAD4 genome AF: 0.215 AC: 32705 AN: 152152 Hom.: 4564 Cov.: 32 AF XY: 0.212 AC XY: 15771 AN XY: 74370

Gnomad4 AFR AF: 0.0551

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.0285

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.227

Alfa AF: 0.279 Hom.: 13686

Bravo AF: 0.206

TwinsUK AF: 0.328 AC: 1216

ALSPAC AF: 0.313 AC: 1208

ESP6500AA AF: 0.0613 AC: 270

ESP6500EA AF: 0.307 AC: 2637

ExAC AF: 0.232 AC: 28211

Asia WGS AF: 0.0770 AC: 271 AN: 3478

EpiCase AF: 0.297

EpiControl AF: 0.301

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.29
DANN	Benign	0.91
DEOGEN2	Benign	0.0016	.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.71	T;T
MetaRNN	Benign	0.0049	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.34	N;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.40	N;N
REVEL	Benign	0.019
Sift	Benign	0.34	T;T
Polyphen		0.078	B;B
Vest4		0.047
MPC		0.43
ClinPred		0.0016	T
GERP RS		-1.6
Varity_R		0.039
gMVP		0.38

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: rs12750774; hg19: chr1-154516477; COSMIC: COSV52724352; COSMIC: COSV52724352;