NM_182499.4:c.542G>A

Variant names:

• chr1-154544001-G-A
• rs12750774
• NM_182499.4:c.542G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182499.4(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. 15/21 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: 𝑓 0.21 (4564 hom., cov: 32)
  • Exomes 𝑓: 0.28 (62241 hom.)
• Consequence: TDRD10 NM_182499.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462
• Publications: 36 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182499.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRD10	NM_182499.4	MANE Select	c.542G>A	p.Arg181Gln	missense	Exon 9 of 13	NP_872305.3
	TDRD10	NM_001098475.2		c.542G>A	p.Arg181Gln	missense	Exon 9 of 12	NP_001091945.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRD10	ENST00000368482.8	TSL:1 MANE Select	c.542G>A	p.Arg181Gln	missense	Exon 9 of 13	ENSP00000357467.4
	TDRD10	ENST00000479937.5	TSL:1	n.287G>A		non_coding_transcript_exon	Exon 4 of 8
	TDRD10	ENST00000368480.3	TSL:2	c.542G>A	p.Arg181Gln	missense	Exon 9 of 12	ENSP00000357465.3

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

GnomAD2 exomes AF: 0.236 AC: 59225 AN: 251394 AF XY: 0.238

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 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

African (AFR) AF: 0.0467 AC: 1562 AN: 33478

American (AMR) AF: 0.247 AC: 11047 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 6497 AN: 26120

East Asian (EAS) AF: 0.0411 AC: 1630 AN: 39698

South Asian (SAS) AF: 0.146 AC: 12607 AN: 86256

European-Finnish (FIN) AF: 0.289 AC: 15445 AN: 53410

Middle Eastern (MID) AF: 0.207 AC: 1194 AN: 5768

European-Non Finnish (NFE) AF: 0.312 AC: 347185 AN: 1111942

Other (OTH) AF: 0.251 AC: 15158 AN: 60388

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

African (AFR) AF: 0.0551 AC: 2291 AN: 41542

American (AMR) AF: 0.260 AC: 3975 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 882 AN: 3468

East Asian (EAS) AF: 0.0285 AC: 148 AN: 5184

South Asian (SAS) AF: 0.134 AC: 649 AN: 4826

European-Finnish (FIN) AF: 0.292 AC: 3096 AN: 10586

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20764 AN: 67940

Other (OTH) AF: 0.227 AC: 479 AN: 2114

Alfa AF: 0.272 Hom.: 25606

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 v4.9

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
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.46
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.019
Sift	Benign	0.34	T
Polyphen		0.078	B
Vest4		0.047
MPC		0.43
ClinPred		0.0016	T
GERP RS		-1.6
Varity_R		0.039
gMVP		0.38
Mutation Taster		=100/0	polymorphism (auto)

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