chr21-42071330-C-T

Position:

chr21-42071330-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001004416.3(UMODL1):c.14C>T(p.Ser5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000953 in 1,594,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

UMODL1
NM_001004416.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.411

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029528618).

BP6

Variant 21-42071330-C-T is Benign according to our data. Variant chr21-42071330-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2378124.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UMODL1	NM_001004416.3 linkuse as main transcript	c.14C>T	p.Ser5Leu	missense_variant	1/23	ENST00000408910.7
UMODL1	NM_173568.4 linkuse as main transcript	c.14C>T	p.Ser5Leu	missense_variant	1/22
UMODL1	NM_001199527.3 linkuse as main transcript	c.-140-4675C>T		intron_variant
UMODL1	NM_001199528.4 linkuse as main transcript	c.-140-4675C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UMODL1	ENST00000408910.7 linkuse as main transcript	c.14C>T	p.Ser5Leu	missense_variant	1/23	1	NM_001004416.3	P2	Q5DID0-1
UMODL1	ENST00000408989.6 linkuse as main transcript	c.14C>T	p.Ser5Leu	missense_variant	1/22	1		A2	Q5DID0-2
UMODL1	ENST00000400424.6 linkuse as main transcript	c.-140-4675C>T		intron_variant		1		A2	Q5DID0-3
UMODL1	ENST00000400427.5 linkuse as main transcript	c.-140-4675C>T		intron_variant		1		A2	Q5DID0-4

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000520

AC:

AN:

230790

Hom.:

AF XY:

0.0000874

AC XY:

AN XY:

125798

show subpopulations

Gnomad AFR exome

AF:

0.0000710

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000719

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000849

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000999

AC:

144

AN:

1441936

Hom.:

Cov.:

AF XY:

0.0000963

AC XY:

AN XY:

716600

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000360

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000108

Gnomad4 OTH exome

AF:

0.000369

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000955

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000361

AC:

ExAC

AF:

0.0000662

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

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

0.051

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.60

CADD

Benign

1.1

DANN

Benign

0.36

DEOGEN2

Benign

0.0011

.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00068

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.0083

MetaRNN

Benign

0.030

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.90

N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

0.57

N;N

REVEL

Benign

0.034

Sift

Benign

0.89

T;T

Sift4G

Benign

0.39

T;T

Polyphen

0.0

B;B

Vest4

0.14

MVP

0.12

MPC

0.091

ClinPred

0.012

GERP RS

-0.18

Varity_R

0.025

gMVP

0.23

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over