rs1012997

Variant names:

• chr7-7663948-A-C
• rs1012997
• NM_001302348.2:c.-63-9361A>C

Variant summary

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

The NM_001302348.2(UMAD1):​c.-63-9361A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 152,134 control chromosomes in the GnomAD database, including 53,275 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 0.84 (53275 hom., cov: 31)
• Consequence: UMAD1 NM_001302348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206
• Publications: 7 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMAD1	NM_001302348.2	c.-63-9361A>C		intron_variant	Intron 1 of 3	ENST00000682710.1	NP_001289277.1
RPA3	NM_002947.5	c.-758+21882T>G		intron_variant	Intron 4 of 7	ENST00000223129.8	NP_002938.1
UMAD1	NM_001302349.2	c.-56-9368A>C		intron_variant	Intron 1 of 3		NP_001289278.1
UMAD1	NM_001302350.2	c.-275-9361A>C		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.-63-9361A>C		intron_variant	Intron 1 of 3		NM_001302348.2	ENSP00000507605.1
RPA3	ENST00000223129.8	c.-758+21882T>G		intron_variant	Intron 4 of 7	1	NM_002947.5	ENSP00000223129.4

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127033 AN: 152016 Hom.: 53254 Cov.: 31

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.879

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.835 AC: 127106 AN: 152134 Hom.: 53275 Cov.: 31 AF XY: 0.830 AC XY: 61758 AN XY: 74378

African (AFR) AF: 0.763 AC: 31660 AN: 41502

American (AMR) AF: 0.863 AC: 13190 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3151 AN: 3470

East Asian (EAS) AF: 0.876 AC: 4537 AN: 5182

South Asian (SAS) AF: 0.776 AC: 3739 AN: 4816

European-Finnish (FIN) AF: 0.792 AC: 8384 AN: 10580

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.879 AC: 59757 AN: 67990

Other (OTH) AF: 0.848 AC: 1792 AN: 2114

Alfa AF: 0.871 Hom.: 96572

Bravo AF: 0.841

Asia WGS AF: 0.776 AC: 2699 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.8
DANN	Benign	0.75
PhyloP100		-0.21
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: rs1012997; hg19: chr7-7703579;