Variant 21-42127763-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000408910.7(UMODL1):c.3622G>A(p.Asp1208Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,613,798 control chromosomes in the GnomAD database, including 101,485 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.35 ( 9449 hom., cov: 33)

Exomes 𝑓: 0.35 ( 92036 hom. )

Consequence

UMODL1
ENST00000408910.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.909

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:

UMODL1 (HGNC:):

UMODL1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004284829).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMODL1	NM_001004416.3 linkuse as main transcript	c.3622G>A	p.Asp1208Asn	missense_variant	20/23	ENST00000408910.7	NP_001004416.3	Q5DID0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7 linkuse as main transcript	c.3622G>A	p.Asp1208Asn	missense_variant	20/23	1	NM_001004416.3	ENSP00000386147.2		Q5DID0-1

Frequencies

GnomAD3 genomes

AF:

0.349

AC:

53069

AN:

151910

Hom.:

9433

Cov.:

show subpopulations

Gnomad AFR

AF:

0.311

Gnomad AMI

AF:

0.434

Gnomad AMR

AF:

0.413

Gnomad ASJ

AF:

0.397

Gnomad EAS

AF:

0.381

Gnomad SAS

AF:

0.361

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.351

Gnomad OTH

AF:

0.355

GnomAD3 exomes

AF:

0.369

AC:

92025

AN:

249488

Hom.:

17282

AF XY:

0.368

AC XY:

49789

AN XY:

135342

show subpopulations

Gnomad AFR exome

AF:

0.312

Gnomad AMR exome

AF:

0.446

Gnomad ASJ exome

AF:

0.398

Gnomad EAS exome

AF:

0.381

Gnomad SAS exome

AF:

0.360

Gnomad FIN exome

AF:

0.346

Gnomad NFE exome

AF:

0.355

Gnomad OTH exome

AF:

0.369

GnomAD4 exome

AF:

0.354

AC:

516856

AN:

1461770

Hom.:

92036

Cov.:

AF XY:

0.353

AC XY:

256859

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.304

Gnomad4 AMR exome

AF:

0.438

Gnomad4 ASJ exome

AF:

0.398

Gnomad4 EAS exome

AF:

0.357

Gnomad4 SAS exome

AF:

0.357

Gnomad4 FIN exome

AF:

0.345

Gnomad4 NFE exome

AF:

0.350

Gnomad4 OTH exome

AF:

0.358

GnomAD4 genome

AF:

0.349

AC:

53133

AN:

152028

Hom.:

9449

Cov.:

AF XY:

0.352

AC XY:

26132

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.312

Gnomad4 AMR

AF:

0.414

Gnomad4 ASJ

AF:

0.397

Gnomad4 EAS

AF:

0.381

Gnomad4 SAS

AF:

0.362

Gnomad4 FIN

AF:

0.345

Gnomad4 NFE

AF:

0.351

Gnomad4 OTH

AF:

0.356

Alfa

AF:

0.355

Hom.:

12894

Bravo

AF:

0.354

TwinsUK

AF:

0.341

AC:

1263

ALSPAC

AF:

0.357

AC:

1375

ESP6500AA

AF:

0.307

AC:

1242

ESP6500EA

AF:

0.352

AC:

2939

ExAC

AF:

0.365

AC:

44136

Asia WGS

AF:

0.355

AC:

1234

AN:

3478

EpiCase

AF:

0.359

EpiControl

AF:

0.355

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.12

DEOGEN2

Benign

0.064

.;.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.092

LIST_S2

Benign

0.12

T;T;T;T

MetaRNN

Benign

0.0043

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-2.0

.;.;.;N

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Uncertain

0.51

PROVEAN

Benign

2.9

N;N;N;N

REVEL

Benign

0.23

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0, 0.0010

.;.;B;B

Vest4

0.10

MPC

0.10

ClinPred

0.0023

GERP RS

2.4

Varity_R

0.031

gMVP

0.21

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over