rs12538804

Variant names:

• chr7-7654288-A-G
• rs12538804
• NM_001302348.2:c.-64+13467A>G

Variant summary

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

The NM_001302348.2(UMAD1):​c.-64+13467A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,032 control chromosomes in the GnomAD database, including 7,523 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 0.30 (7523 hom., cov: 32)
• Consequence: UMAD1 NM_001302348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.599
• Publications: 5 publications found

Genes affected

UMAD1 (HGNC:48955): (UBAP1-MVB12-associated (UMA) domain containing 1)

RPA3 (HGNC:10291): (replication protein A3) Enables damaged DNA binding activity and single-stranded DNA binding activity. Involved in DNA repair and DNA replication. Part of DNA replication factor A complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000283549 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMAD1	NM_001302348.2	c.-64+13467A>G		intron_variant	Intron 1 of 3	ENST00000682710.1	NP_001289277.1
RPA3	NM_002947.5	c.-757-13113T>C		intron_variant	Intron 4 of 7	ENST00000223129.8	NP_002938.1
UMAD1	NM_001302349.2	c.-57+13467A>G		intron_variant	Intron 1 of 3		NP_001289278.1
UMAD1	NM_001302350.2	c.-276+13467A>G		intron_variant	Intron 1 of 4		NP_001289279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMAD1	ENST00000682710.1	c.-64+13467A>G		intron_variant	Intron 1 of 3		NM_001302348.2	ENSP00000507605.1
RPA3	ENST00000223129.8	c.-757-13113T>C		intron_variant	Intron 4 of 7	1	NM_002947.5	ENSP00000223129.4

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45294 AN: 151914 Hom.: 7511 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.0881

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.268

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.298 AC: 45339 AN: 152032 Hom.: 7523 Cov.: 32 AF XY: 0.299 AC XY: 22214 AN XY: 74310

African (AFR) AF: 0.443 AC: 18339 AN: 41434

American (AMR) AF: 0.318 AC: 4865 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 916 AN: 3468

East Asian (EAS) AF: 0.0877 AC: 453 AN: 5166

South Asian (SAS) AF: 0.188 AC: 908 AN: 4818

European-Finnish (FIN) AF: 0.288 AC: 3044 AN: 10578

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16103 AN: 67966

Other (OTH) AF: 0.265 AC: 560 AN: 2112

Alfa AF: 0.270 Hom.: 1461

Bravo AF: 0.309

Asia WGS AF: 0.155 AC: 543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.70
PhyloP100		-0.60
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: rs12538804; hg19: chr7-7693919;