17-35918397-T-C

Variant names:

• chr17-35918397-T-C
• rs138443064
• NM_145654.4:c.800A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145654.4(RDM1):​c.800A>G​(p.Tyr267Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. Y267F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RDM1 NM_145654.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376
• Publications: 0 publications found

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]

ENSG00000270240 (HGNC:58767):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059395015).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145654.4. 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
	RDM1	NM_145654.4	MANE Select	c.800A>G	p.Tyr267Cys	missense	Exon 7 of 7	NP_663629.1	Q8NG50-1
	RDM1	NM_001163130.1		c.731A>G	p.Tyr244Cys	missense	Exon 6 of 6	NP_001156602.1	Q8NG50-2
	RDM1	NM_001163121.2		c.701A>G	p.Tyr234Cys	missense	Exon 6 of 6	NP_001156593.1	Q8NG50-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDM1	ENST00000620284.5	TSL:1 MANE Select	c.800A>G	p.Tyr267Cys	missense	Exon 7 of 7	ENSP00000483549.1	Q8NG50-1
	RDM1	ENST00000619262.4	TSL:1	c.731A>G	p.Tyr244Cys	missense	Exon 6 of 6	ENSP00000479310.1	Q8NG50-2
	RDM1	ENST00000616596.4	TSL:1	c.701A>G	p.Tyr234Cys	missense	Exon 6 of 6	ENSP00000478915.1	Q8NG50-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461870 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727230

African (AFR) AF: 0.00 AC: 0 AN: 33480

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: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	4.4
DANN	Benign	0.082
DEOGEN2	Benign	0.00056	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0019	N
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.38
PrimateAI	Benign	0.37	T
Sift4G	Benign	0.14	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.17		Loss of phosphorylation at Y267 (P = 0.0394)
MVP		0.38
ClinPred		0.016	T
GERP RS		-0.043
Varity_R		0.044
gMVP		0.037

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: rs138443064; hg19: chr17-34245401;