chr17-35930065-T-A

Position:

• chr17-35930065-T-A

Variant summary

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

The NM_145654.4(RDM1):​c.276+11A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,607,872 control chromosomes in the GnomAD database, including 21,430 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.

• Frequency:
  • Genomes: 𝑓 0.16 (1991 hom., cov: 32)
  • Exomes 𝑓: 0.16 (19439 hom.)
• Consequence: RDM1 NM_145654.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.775

Genes affected

RDM1 (HGNC:19950): (RAD52 motif containing 1) This gene encodes a protein involved in the cellular response to cisplatin, a drug commonly used in chemotherapy. The protein encoded by this gene contains two motifs: a motif found in RAD52, a protein that functions in DNA double-strand breaks and homologous recombination, and an RNA recognition motif (RRM) that is not found in RAD52. The RAD52 motif region in RAD52 is important for protein function and may be involved in DNA binding or oligomerization. Alternatively spliced transcript variants encoding different isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RDM1	NM_145654.4	c.276+11A>T		intron_variant		ENST00000620284.5	NP_663629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RDM1	ENST00000620284.5	c.276+11A>T		intron_variant		1	NM_145654.4	ENSP00000483549	P1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23677 AN: 152172 Hom.: 1986 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.154

GnomAD3 exomes AF: 0.180 AC: 44678 AN: 248888 Hom.: 4410 AF XY: 0.180 AC XY: 24262 AN XY: 134734

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.242

Gnomad ASJ exome AF: 0.182

Gnomad EAS exome AF: 0.213

Gnomad SAS exome AF: 0.260

Gnomad FIN exome AF: 0.142

Gnomad NFE exome AF: 0.147

Gnomad OTH exome AF: 0.169

GnomAD4 exome AF: 0.159 AC: 231183 AN: 1455582 Hom.: 19439 Cov.: 31 AF XY: 0.161 AC XY: 116721 AN XY: 723836

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.232

Gnomad4 ASJ exome AF: 0.186

Gnomad4 EAS exome AF: 0.209

Gnomad4 SAS exome AF: 0.260

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.147

Gnomad4 OTH exome AF: 0.159

GnomAD4 genome AF: 0.156 AC: 23713 AN: 152290 Hom.: 1991 Cov.: 32 AF XY: 0.159 AC XY: 11808 AN XY: 74466

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.153

Alfa AF: 0.152 Hom.: 352

Bravo AF: 0.157

Asia WGS AF: 0.233 AC: 808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.2
DANN	Benign	0.65

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: rs9913559; hg19: chr17-34257069;