rs220159

chr21-42127763-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004416.3(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 NM_001004416.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.909

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]

ACMG classification

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	UniProt
UMODL1	NM_001004416.3	c.3622G>A	p.Asp1208Asn	missense_variant	20/23	ENST00000408910.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UMODL1	ENST00000408910.7	c.3622G>A	p.Asp1208Asn	missense_variant	20/23	1	NM_001004416.3	P2

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53069 AN: 151910 Hom.: 9433 Cov.: 33

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

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.: 49 AF XY: 0.353 AC XY: 256859 AN XY: 727186

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.: 33 AF XY: 0.352 AC XY: 26132 AN XY: 74290

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	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	12
Dann	Benign	0.12
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.12	T;T;T;T
MetaRNN	Benign	0.0043	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Uncertain	0.51	T
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	T
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

Other links and lift over

dbSNP: rs220159; hg19: chr21-43547873; COSMIC: COSV68569225; COSMIC: COSV68569225;