21-42076196-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001004416.3(UMODL1):c.268G>A(p.Val90Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,614,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

UMODL1
NM_001004416.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.537

Publications

2 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11079064).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMODL1	NM_001004416.3 link	c.268G>A	p.Val90Met	missense_variant	Exon 2 of 23	ENST00000408910.7	NP_001004416.3	Q5DID0-1
UMODL1	NM_173568.4 link	c.268G>A	p.Val90Met	missense_variant	Exon 2 of 22		NP_775839.4	Q5DID0-2
UMODL1	NM_001199527.3 link	c.52G>A	p.Val18Met	missense_variant	Exon 2 of 22		NP_001186456.2	Q5DID0-4
UMODL1	NM_001199528.4 link	c.52G>A	p.Val18Met	missense_variant	Exon 2 of 23		NP_001186457.3	Q5DID0-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UMODL1	ENST00000408910.7 link	c.268G>A	p.Val90Met	missense_variant	Exon 2 of 23	1	NM_001004416.3	ENSP00000386147.2	Q5DID0-1
UMODL1	ENST00000408989.6 link	c.268G>A	p.Val90Met	missense_variant	Exon 2 of 22	1		ENSP00000386126.2	Q5DID0-2
UMODL1	ENST00000400427.5 link	c.52G>A	p.Val18Met	missense_variant	Exon 2 of 22	1		ENSP00000383279.1	Q5DID0-4
UMODL1	ENST00000400424.6 link	c.52G>A	p.Val18Met	missense_variant	Exon 2 of 23	1		ENSP00000383276.1	Q5DID0-3

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000361

AC:

AN:

249532

AF XY:

0.000347

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.000689

Gnomad OTH exome

AF:

0.000495

GnomAD4 exome

AF:

0.000136

AC:

199

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000133

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.0000894

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.000126

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000431

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000128

AC:

142

AN:

1112010

Other (OTH)

AF:

0.000315

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000164

AC:

AN:

152364

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74516

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41590

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000771

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000213

Hom.:

Bravo

AF:

0.000147

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000355

AC:

ExAC

AF:

0.000619

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 17, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.268G>A (p.V90M) alteration is located in exon 2 (coding exon 2) of the UMODL1 gene. This alteration results from a G to A substitution at nucleotide position 268, causing the valine (V) at amino acid position 90 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.048

.;.;.;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.69

T;T;T;T

M_CAP

Benign

0.037

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.4

.;.;M;M

PhyloP100

0.54

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.080

T;T;T;T

Sift4G

Uncertain

0.045

D;T;T;T

Polyphen

1.0, 1.0

.;.;D;D

Vest4

0.48

MVP

0.66

MPC

0.41

ClinPred

0.093

GERP RS

1.4

Varity_R

0.027

gMVP

0.28

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

21-42076196-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over