Variant chr21-42076183-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001004416.3(UMODL1):c.255C>T(p.Pro85=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,614,218 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0026 ( 10 hom. )

Consequence

UMODL1
NM_001004416.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.78

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 21-42076183-C-T is Benign according to our data. Variant chr21-42076183-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2652695.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.78 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UMODL1	NM_001004416.3 linkuse as main transcript	c.255C>T	p.Pro85=	synonymous_variant	2/23	ENST00000408910.7
UMODL1	NM_173568.4 linkuse as main transcript	c.255C>T	p.Pro85=	synonymous_variant	2/22
UMODL1	NM_001199527.3 linkuse as main transcript	c.39C>T	p.Pro13=	synonymous_variant	2/22
UMODL1	NM_001199528.4 linkuse as main transcript	c.39C>T	p.Pro13=	synonymous_variant	2/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UMODL1	ENST00000408910.7 linkuse as main transcript	c.255C>T	p.Pro85=	synonymous_variant	2/23	1	NM_001004416.3	P2	Q5DID0-1
UMODL1	ENST00000408989.6 linkuse as main transcript	c.255C>T	p.Pro85=	synonymous_variant	2/22	1		A2	Q5DID0-2
UMODL1	ENST00000400427.5 linkuse as main transcript	c.39C>T	p.Pro13=	synonymous_variant	2/22	1		A2	Q5DID0-4
UMODL1	ENST00000400424.6 linkuse as main transcript	c.39C>T	p.Pro13=	synonymous_variant	2/23	1		A2	Q5DID0-3

Frequencies

GnomAD3 genomes

AF:

0.00155

AC:

236

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00262

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00179

AC:

447

AN:

249540

Hom.:

AF XY:

0.00191

AC XY:

259

AN XY:

135396

show subpopulations

Gnomad AFR exome

AF:

0.000904

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000686

Gnomad FIN exome

AF:

0.00209

Gnomad NFE exome

AF:

0.00280

Gnomad OTH exome

AF:

0.00198

GnomAD4 exome

AF:

0.00264

AC:

3855

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00257

AC XY:

1872

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000939

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000823

Gnomad4 FIN exome

AF:

0.00256

Gnomad4 NFE exome

AF:

0.00310

Gnomad4 OTH exome

AF:

0.00238

GnomAD4 genome

AF:

0.00155

AC:

236

AN:

152326

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00262

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00201

Hom.:

Bravo

AF:

0.00159

EpiCase

AF:

0.00251

EpiControl

AF:

0.00243

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

May 01, 2022

UMODL1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.21

DANN

Benign

0.70

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