rs3819141

Variant names:

• chr21-42137449-T-A
• rs3819141
• NM_001004416.3:c.3786T>A

Your query was ambiguous. Multiple possible variants found:

• chr21-42137449-T-A
• chr21-42137449-T-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001004416.3(UMODL1):​c.3786T>A​(p.Pro1262Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,613,920 control chromosomes in the GnomAD database, including 110,668 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (8875 hom., cov: 34)
  • Exomes 𝑓: 0.37 (101793 hom.)
• Consequence: UMODL1 NM_001004416.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 14 publications found

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]

ENSG00000304334 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP7: Synonymous conserved (PhyloP=-1.4 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004416.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UMODL1	NM_001004416.3	MANE Select	c.3786T>A	p.Pro1262Pro	synonymous	Exon 22 of 23	NP_001004416.3	Q5DID0-1
	UMODL1	NM_173568.4		c.4170T>A	p.Pro1390Pro	synonymous	Exon 21 of 22	NP_775839.4
	UMODL1	NM_001199527.3		c.3954T>A	p.Pro1318Pro	synonymous	Exon 21 of 22	NP_001186456.2	Q5DID0-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UMODL1	ENST00000408910.7	TSL:1 MANE Select	c.3786T>A	p.Pro1262Pro	synonymous	Exon 22 of 23	ENSP00000386147.2	Q5DID0-1
	UMODL1	ENST00000408989.6	TSL:1	c.4170T>A	p.Pro1390Pro	synonymous	Exon 21 of 22	ENSP00000386126.2	Q5DID0-2
	UMODL1	ENST00000400427.5	TSL:1	c.3954T>A	p.Pro1318Pro	synonymous	Exon 21 of 22	ENSP00000383279.1	Q5DID0-4

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50869 AN: 152106 Hom.: 8867 Cov.: 34

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.325

GnomAD2 exomes AF: 0.377 AC: 94141 AN: 249482 AF XY: 0.383

Gnomad AFR exome AF: 0.219

Gnomad AMR exome AF: 0.374

Gnomad ASJ exome AF: 0.394

Gnomad EAS exome AF: 0.401

Gnomad FIN exome AF: 0.422

Gnomad NFE exome AF: 0.372

Gnomad OTH exome AF: 0.364

GnomAD4 exome AF: 0.371 AC: 542266 AN: 1461696 Hom.: 101793 Cov.: 53 AF XY: 0.374 AC XY: 271809 AN XY: 727156

African (AFR) AF: 0.215 AC: 7197 AN: 33478

American (AMR) AF: 0.372 AC: 16622 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 10289 AN: 26136

East Asian (EAS) AF: 0.425 AC: 16856 AN: 39694

South Asian (SAS) AF: 0.430 AC: 37062 AN: 86252

European-Finnish (FIN) AF: 0.418 AC: 22326 AN: 53370

Middle Eastern (MID) AF: 0.404 AC: 2322 AN: 5750

European-Non Finnish (NFE) AF: 0.366 AC: 407342 AN: 1111904

Other (OTH) AF: 0.368 AC: 22250 AN: 60388

GnomAD4 genome AF: 0.334 AC: 50888 AN: 152224 Hom.: 8875 Cov.: 34 AF XY: 0.337 AC XY: 25062 AN XY: 74420

African (AFR) AF: 0.216 AC: 8991 AN: 41554

American (AMR) AF: 0.363 AC: 5545 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1348 AN: 3472

East Asian (EAS) AF: 0.414 AC: 2143 AN: 5172

South Asian (SAS) AF: 0.424 AC: 2047 AN: 4826

European-Finnish (FIN) AF: 0.416 AC: 4400 AN: 10586

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25299 AN: 68004

Other (OTH) AF: 0.326 AC: 689 AN: 2114

Alfa AF: 0.364 Hom.: 3364

Bravo AF: 0.325

Asia WGS AF: 0.393 AC: 1365 AN: 3478

EpiCase AF: 0.375

EpiControl AF: 0.370

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.089
DANN	Benign	0.46
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3819141; hg19: chr21-43557559; COSMIC: COSV68569410;