Variant rs3819142 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001004416.3(UMODL1):c.3925A>C(p.Asn1309His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,613,724 control chromosomes in the GnomAD database, including 29,240 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.19 ( 2661 hom., cov: 32)

Exomes 𝑓: 0.19 ( 26579 hom. )

Consequence

UMODL1
NM_001004416.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.63

Variant links:

Genes affected

UMODL1 (HGNC:12560): (uromodulin like 1) Predicted to be an extracellular matrix structural constituent. Predicted to be involved in neutrophil migration. Predicted to act upstream of or within several processes, including adipose tissue development; cellular response to gonadotropin-releasing hormone; and regulation of ovarian follicle development. Predicted to be located in cytoplasm and external side of plasma membrane. Predicted to be integral component of membrane. Predicted to be active in apical plasma membrane; cell surface; and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

UMODL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0056490004).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UMODL1	NM_001004416.3 linkuse as main transcript	c.3925A>C	p.Asn1309His	missense_variant	22/23	ENST00000408910.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UMODL1	ENST00000408910.7 linkuse as main transcript	c.3925A>C	p.Asn1309His	missense_variant	22/23	1	NM_001004416.3	P2	Q5DID0-1

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28386

AN:

151870

Hom.:

2657

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.294

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.178

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.304

Gnomad FIN

AF:

0.227

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.175

GnomAD3 exomes

AF:

0.208

AC:

51821

AN:

249476

Hom.:

5554

AF XY:

0.211

AC XY:

28502

AN XY:

135356

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.219

Gnomad ASJ exome

AF:

0.182

Gnomad EAS exome

AF:

0.238

Gnomad SAS exome

AF:

0.293

Gnomad FIN exome

AF:

0.229

Gnomad NFE exome

AF:

0.181

Gnomad OTH exome

AF:

0.193

GnomAD4 exome

AF:

0.187

AC:

273843

AN:

1461736

Hom.:

26579

Cov.:

AF XY:

0.191

AC XY:

138776

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.169

Gnomad4 AMR exome

AF:

0.218

Gnomad4 ASJ exome

AF:

0.181

Gnomad4 EAS exome

AF:

0.222

Gnomad4 SAS exome

AF:

0.289

Gnomad4 FIN exome

AF:

0.226

Gnomad4 NFE exome

AF:

0.175

Gnomad4 OTH exome

AF:

0.194

GnomAD4 genome

AF:

0.187

AC:

28393

AN:

151988

Hom.:

2661

Cov.:

AF XY:

0.189

AC XY:

14073

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.161

Gnomad4 AMR

AF:

0.206

Gnomad4 ASJ

AF:

0.178

Gnomad4 EAS

AF:

0.233

Gnomad4 SAS

AF:

0.302

Gnomad4 FIN

AF:

0.227

Gnomad4 NFE

AF:

0.180

Gnomad4 OTH

AF:

0.174

Alfa

AF:

0.181

Hom.:

6230

Bravo

AF:

0.184

TwinsUK

AF:

0.164

AC:

608

ALSPAC

AF:

0.168

AC:

647

ESP6500AA

AF:

0.157

AC:

640

ESP6500EA

AF:

0.180

AC:

1507

ExAC

AF:

0.208

AC:

25197

Asia WGS

AF:

0.256

AC:

890

AN:

3478

EpiCase

AF:

0.179

EpiControl

AF:

0.179

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.0085

.;.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.66

T;T;T;T

MetaRNN

Benign

0.0056

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;.;.;N

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.3

N;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.054

T;D;T;D

Sift4G

Uncertain

0.0040

D;D;D;D

Polyphen

0.68, 0.80

.;.;P;P

Vest4

0.096

MPC

0.41

ClinPred

0.013

GERP RS

1.2

Varity_R

0.043

gMVP

0.52

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over