21-42071353-G-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004416.3(UMODL1):c.37G>T(p.Val13Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000553 in 1,445,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

UMODL1
NM_001004416.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.340

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15428576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMODL1	NM_001004416.3 link	c.37G>T	p.Val13Phe	missense_variant	Exon 1 of 23	ENST00000408910.7	NP_001004416.3	Q5DID0-1
UMODL1	NM_173568.4 link	c.37G>T	p.Val13Phe	missense_variant	Exon 1 of 22		NP_775839.4	Q5DID0-2
UMODL1	NM_001199527.3 link	c.-140-4652G>T		intron_variant	Intron 1 of 21		NP_001186456.2	Q5DID0-4
UMODL1	NM_001199528.4 link	c.-140-4652G>T		intron_variant	Intron 1 of 22		NP_001186457.3	Q5DID0-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UMODL1	ENST00000408910.7 link	c.37G>T	p.Val13Phe	missense_variant	Exon 1 of 23	1	NM_001004416.3	ENSP00000386147.2	Q5DID0-1
UMODL1	ENST00000408989.6 link	c.37G>T	p.Val13Phe	missense_variant	Exon 1 of 22	1		ENSP00000386126.2	Q5DID0-2
UMODL1	ENST00000400427.5 link	c.-140-4652G>T		intron_variant	Intron 1 of 21	1		ENSP00000383279.1	Q5DID0-4
UMODL1	ENST00000400424.6 link	c.-140-4652G>T		intron_variant	Intron 1 of 22	1		ENSP00000383276.1	Q5DID0-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

232908

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000553

AC:

AN:

1445796

Hom.:

Cov.:

AF XY:

0.00000696

AC XY:

AN XY:

718780

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32522

American (AMR)

AF:

0.00

AC:

AN:

42498

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25810

East Asian (EAS)

AF:

0.00

AC:

AN:

38102

South Asian (SAS)

AF:

0.00

AC:

AN:

83778

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52976

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.00000724

AC:

AN:

1104602

Other (OTH)

AF:

0.00

AC:

AN:

59790

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 10, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.37G>T (p.V13F) alteration is located in exon 1 (coding exon 1) of the UMODL1 gene. This alteration results from a G to T substitution at nucleotide position 37, causing the valine (V) at amino acid position 13 to be replaced by a phenylalanine (F). 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

0.081

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0039

.;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.55

N;N

PhyloP100

0.34

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.91

N;N

REVEL

Benign

0.14

Sift

Benign

0.059

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.93

P;P

Vest4

0.24

MutPred

0.44

Loss of helix (P = 0.0041);Loss of helix (P = 0.0041);

MVP

0.41

MPC

0.38

ClinPred

0.28

GERP RS

0.47

PromoterAI

-0.0014

Neutral

(source)

Varity_R

0.091

gMVP

0.54

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

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21-42071353-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over