Variant chr21-42084188-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001004416.3(UMODL1):c.424C>T(p.Leu142Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000417 in 1,614,014 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 3 hom. )

Consequence

UMODL1
NM_001004416.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.27

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00958392).

BP6

Variant 21-42084188-C-T is Benign according to our data. Variant chr21-42084188-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3025392.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UMODL1	NM_001004416.3 linkuse as main transcript	c.424C>T	p.Leu142Phe	missense_variant	3/23	ENST00000408910.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UMODL1	ENST00000408910.7 linkuse as main transcript	c.424C>T	p.Leu142Phe	missense_variant	3/23	1	NM_001004416.3	P2	Q5DID0-1
UMODL1	ENST00000408989.6 linkuse as main transcript	c.424C>T	p.Leu142Phe	missense_variant	3/22	1		A2	Q5DID0-2
UMODL1	ENST00000400427.5 linkuse as main transcript	c.208C>T	p.Leu70Phe	missense_variant	3/22	1		A2	Q5DID0-4
UMODL1	ENST00000400424.6 linkuse as main transcript	c.208C>T	p.Leu70Phe	missense_variant	3/23	1		A2	Q5DID0-3

Frequencies

GnomAD3 genomes

AF:

0.00209

AC:

318

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00702

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000545

AC:

136

AN:

249468

Hom.:

AF XY:

0.000458

AC XY:

AN XY:

135368

show subpopulations

Gnomad AFR exome

AF:

0.00724

Gnomad AMR exome

AF:

0.000493

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000243

AC:

355

AN:

1461684

Hom.:

Cov.:

AF XY:

0.000226

AC XY:

164

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.00672

Gnomad4 AMR exome

AF:

0.000604

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000459

Gnomad4 OTH exome

AF:

0.000695

GnomAD4 genome

AF:

0.00209

AC:

318

AN:

152330

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

142

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00700

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000474

Hom.:

Bravo

AF:

0.00238

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00752

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.000670

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

UMODL1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

.;.;.;T

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.81

T;T;T;T

MetaRNN

Benign

0.0096

T;T;T;T

MetaSVM

Uncertain

-0.091

MutationAssessor

Pathogenic

2.9

.;.;M;M

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-2.2

N;N;N;N

REVEL

Uncertain

0.40

Sift

Benign

0.057

T;T;T;T

Sift4G

Uncertain

0.0090

D;D;D;D

Polyphen

1.0

.;.;D;D

Vest4

0.47

MVP

0.62

MPC

0.46

ClinPred

0.065

GERP RS

3.9

Varity_R

0.11

gMVP

0.21

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over