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GeneBe

21-42076183-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

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

2

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.78 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UMODL1NM_001004416.3 linkuse as main transcriptc.255C>T p.Pro85= synonymous_variant 2/23 ENST00000408910.7
UMODL1NM_173568.4 linkuse as main transcriptc.255C>T p.Pro85= synonymous_variant 2/22
UMODL1NM_001199527.3 linkuse as main transcriptc.39C>T p.Pro13= synonymous_variant 2/22
UMODL1NM_001199528.4 linkuse as main transcriptc.39C>T p.Pro13= synonymous_variant 2/23

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UMODL1ENST00000408910.7 linkuse as main transcriptc.255C>T p.Pro85= synonymous_variant 2/231 NM_001004416.3 P2Q5DID0-1
UMODL1ENST00000408989.6 linkuse as main transcriptc.255C>T p.Pro85= synonymous_variant 2/221 A2Q5DID0-2
UMODL1ENST00000400427.5 linkuse as main transcriptc.39C>T p.Pro13= synonymous_variant 2/221 A2Q5DID0-4
UMODL1ENST00000400424.6 linkuse as main transcriptc.39C>T p.Pro13= synonymous_variant 2/231 A2Q5DID0-3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00155
AC:
236
AN:
152208
Hom.:
0
Cov.:
34
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.:
1
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.:
10
Cov.:
32
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00155
AC:
236
AN:
152326
Hom.:
0
Cov.:
34
AF XY:
0.00113
AC XY:
84
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.:
0
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 submitterclinical testingCeGaT Center for Human Genetics TuebingenMay 01, 2022UMODL1: 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.

Other links and lift over

dbSNP: rs1537116; hg19: chr21-43496292; API