NM_001004416.3:c.367G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001004416.3(UMODL1):c.367G>A(p.Ala123Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000265 in 1,614,034 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 5 hom. )

Consequence

UMODL1
NM_001004416.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.733

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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050383806).

BP6

Variant 21-42084131-G-A is Benign according to our data. Variant chr21-42084131-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3977571.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMODL1	NM_001004416.3 link	c.367G>A	p.Ala123Thr	missense_variant	Exon 3 of 23	ENST00000408910.7	NP_001004416.3	Q5DID0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UMODL1	ENST00000408910.7 link	c.367G>A	p.Ala123Thr	missense_variant	Exon 3 of 23	1	NM_001004416.3	ENSP00000386147.2	Q5DID0-1
UMODL1	ENST00000408989.6 link	c.367G>A	p.Ala123Thr	missense_variant	Exon 3 of 22	1		ENSP00000386126.2	Q5DID0-2
UMODL1	ENST00000400427.5 link	c.151G>A	p.Ala51Thr	missense_variant	Exon 3 of 22	1		ENSP00000383279.1	Q5DID0-4
UMODL1	ENST00000400424.6 link	c.151G>A	p.Ala51Thr	missense_variant	Exon 3 of 23	1		ENSP00000383276.1	Q5DID0-3

Frequencies

GnomAD3 genomes

AF:

0.000604

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000413

AC:

103

AN:

249398

AF XY:

0.000458

show subpopulations

Gnomad AFR exome

AF:

0.00168

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000229

AC:

334

AN:

1461698

Hom.:

Cov.:

AF XY:

0.000293

AC XY:

213

AN XY:

727160

show subpopulations

African (AFR)

AF:

0.00239

AC:

AN:

33462

American (AMR)

AF:

0.000224

AC:

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00242

AC:

209

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1111944

Other (OTH)

AF:

0.000298

AC:

AN:

60382

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

GnomAD4 genome

AF:

0.000617

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.00190

AC:

AN:

41586

American (AMR)

AF:

0.000196

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2110

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:

0.000384

Hom.:

Bravo

AF:

0.000657

ESP6500AA

AF:

0.00130

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.000488

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Apr 09, 2025

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.010

(source)

DANN

Benign

0.35

DEOGEN2

Benign

0.017

.;.;.;T

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0067

LIST_S2

Benign

0.37

T;T;T;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.0050

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.3

.;.;N;N

PhyloP100

-0.73

PrimateAI

Benign

0.26

PROVEAN

Benign

0.050

N;N;N;N

REVEL

Benign

0.073

Sift

Benign

0.67

T;T;T;T

Sift4G

Benign

0.51

T;T;T;T

Polyphen

0.43, 0.0060

.;.;B;B

Vest4

0.055

MVP

0.014

MPC

0.11

ClinPred

0.0083

GERP RS

-7.7

Varity_R

0.018

gMVP

0.094

Mutation Taster

=89/11

polymorphism

(source)

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

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NM_001004416.3:c.367G>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