NM_134424.4:c.*1042A>C

Variant names:

• chr12-912349-T-G
• rs7963551
• NM_134424.4:c.*1042A>C

Variant summary

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

The NM_134424.4(RAD52):​c.*1042A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 201,738 control chromosomes in the GnomAD database, including 2,112 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 0.13 (1566 hom., cov: 31)
  • Exomes 𝑓: 0.14 (546 hom.)
• Consequence: RAD52 NM_134424.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398
• Publications: 37 publications found

Genes affected

RAD52 (HGNC:9824): (RAD52 homolog, DNA repair protein) The protein encoded by this gene shares similarity with Saccharomyces cerevisiae Rad52, a protein important for DNA double-strand break repair and homologous recombination. This gene product was shown to bind single-stranded DNA ends, and mediate the DNA-DNA interaction necessary for the annealing of complementary DNA strands. It was also found to interact with DNA recombination protein RAD51, which suggested its role in RAD51 related DNA recombination and repair. A pseudogene of this gene is present on chromosome 2. Alternative splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Jul 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_134424.4. 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
	RAD52	NM_134424.4	MANE Select	c.*1042A>C		3_prime_UTR	Exon 12 of 12	NP_602296.2
	RAD52	NR_123713.2		n.2692A>C		non_coding_transcript_exon	Exon 14 of 14
	RAD52	NM_001297419.1		c.*1042A>C		3_prime_UTR	Exon 12 of 12	NP_001284348.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD52	ENST00000358495.8	TSL:1 MANE Select	c.*1042A>C		3_prime_UTR	Exon 12 of 12	ENSP00000351284.3
	RAD52	ENST00000228345.9	TSL:2	n.2632A>C		non_coding_transcript_exon	Exon 11 of 11
	RAD52	ENST00000430095.6	TSL:1	c.*1042A>C		downstream_gene	N/A	ENSP00000387901.2

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19977 AN: 151926 Hom.: 1563 Cov.: 31

Gnomad AFR AF: 0.0498

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.144 AC: 7153 AN: 49694 Hom.: 546 Cov.: 0 AF XY: 0.144 AC XY: 3336 AN XY: 23116

African (AFR) AF: 0.0406 AC: 88 AN: 2170

American (AMR) AF: 0.124 AC: 176 AN: 1418

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 464 AN: 3182

East Asian (EAS) AF: 0.137 AC: 1098 AN: 8014

South Asian (SAS) AF: 0.153 AC: 64 AN: 418

European-Finnish (FIN) AF: 0.188 AC: 6 AN: 32

Middle Eastern (MID) AF: 0.232 AC: 72 AN: 310

European-Non Finnish (NFE) AF: 0.151 AC: 4539 AN: 30024

Other (OTH) AF: 0.157 AC: 646 AN: 4126

GnomAD4 genome AF: 0.131 AC: 19986 AN: 152044 Hom.: 1566 Cov.: 31 AF XY: 0.136 AC XY: 10115 AN XY: 74308

African (AFR) AF: 0.0500 AC: 2076 AN: 41508

American (AMR) AF: 0.125 AC: 1915 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 543 AN: 3470

East Asian (EAS) AF: 0.179 AC: 926 AN: 5170

South Asian (SAS) AF: 0.166 AC: 798 AN: 4818

European-Finnish (FIN) AF: 0.267 AC: 2816 AN: 10538

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10381 AN: 67962

Other (OTH) AF: 0.132 AC: 279 AN: 2112

Alfa AF: 0.141 Hom.: 324

Bravo AF: 0.117

Asia WGS AF: 0.154 AC: 538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.49
PhyloP100		-0.40
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: rs7963551; hg19: chr12-1021515;