17-35930144-C-A

Variant names:

• chr17-35930144-C-A
• NM_145654.4:c.208G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145654.4(RDM1):​c.208G>T​(p.Ala70Ser) 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 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RDM1 NM_145654.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.17
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.086088).

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.208G>T	p.Ala70Ser	missense	Exon 2 of 7	NP_663629.1	Q8NG50-1
	RDM1	NM_001163130.1		c.139G>T	p.Ala47Ser	missense	Exon 1 of 6	NP_001156602.1	Q8NG50-2
	RDM1	NM_001163121.2		c.208G>T	p.Ala70Ser	missense	Exon 2 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.208G>T	p.Ala70Ser	missense	Exon 2 of 7	ENSP00000483549.1	Q8NG50-1
	RDM1	ENST00000619262.4	TSL:1	c.139G>T	p.Ala47Ser	missense	Exon 1 of 6	ENSP00000479310.1	Q8NG50-2
	RDM1	ENST00000616596.4	TSL:1	c.208G>T	p.Ala70Ser	missense	Exon 2 of 6	ENSP00000478915.1	Q8NG50-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727236

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

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.0098	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.063	N
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.2
PrimateAI	Benign	0.44	T
Sift4G	Benign	0.099	T
Polyphen		0.14	B
Vest4		0.34
MutPred		0.23		Gain of disorder (P = 0.0597)
MVP		0.27
ClinPred		0.18	T
GERP RS		2.8
PromoterAI		0.034	Neutral
Varity_R		0.072
gMVP		0.37
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr17-34257148;