Genetic Variant NM_001302348.2:c.-64+568C>T (chr7-7641389-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001302348.2(UMAD1):c.-64+568C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,148 control chromosomes in the GnomAD database, including 6,358 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 0.25 ( 6350 hom., cov: 32)

Exomes 𝑓: 0.37 ( 8 hom. )

Consequence

UMAD1
NM_001302348.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.712

Publications

5 publications found

Variant links:

Genes affected

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

UMAD1 links:

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]

RPA3 links:

ENSG00000283549 (HGNC:):

ENSG00000283549 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001302348.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
UMAD1	NM_001302348.2	MANE Select	c.-64+568C>T	intron	N/A	NP_001289277.1
RPA3	NM_002947.5	MANE Select	c.-757-214G>A	intron	N/A	NP_002938.1
UMAD1	NM_001302349.2		c.-57+568C>T	intron	N/A	NP_001289278.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
UMAD1	ENST00000682710.1	MANE Select	c.-64+568C>T	intron	N/A	ENSP00000507605.1
RPA3	ENST00000223129.8	TSL:1 MANE Select	c.-757-214G>A	intron	N/A	ENSP00000223129.4
UMAD1	ENST00000636849.1	TSL:5	c.-51+568C>T	intron	N/A	ENSP00000489648.1

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38096

AN:

151954

Hom.:

6341

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0672

Gnomad AMI

AF:

0.218

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.292

Gnomad EAS

AF:

0.752

Gnomad SAS

AF:

0.487

Gnomad FIN

AF:

0.348

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.282

Gnomad OTH

AF:

0.246

GnomAD4 exome

AF:

0.368

AC:

AN:

Hom.:

AF XY:

0.367

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.367

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.251

AC:

38114

AN:

152072

Hom.:

6350

Cov.:

AF XY:

0.261

AC XY:

19402

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.0671

AC:

2787

AN:

41544

American (AMR)

AF:

0.290

AC:

4425

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

1013

AN:

3466

East Asian (EAS)

AF:

0.753

AC:

3881

AN:

5154

South Asian (SAS)

AF:

0.487

AC:

2345

AN:

4814

European-Finnish (FIN)

AF:

0.348

AC:

3664

AN:

10538

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.282

AC:

19195

AN:

67954

Other (OTH)

AF:

0.249

AC:

527

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1321

2641

3962

5282

6603

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

400

800

1200

1600

2000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.274

Hom.:

10060

Bravo

AF:

0.236

Asia WGS

AF:

0.565

AC:

1964

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

9.1

(source)

DANN

Benign

0.77

PhyloP100

0.71

PromoterAI

0.014

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over