21-42102239-T-C

Variant names:

• chr21-42102239-T-C
• rs220109
• NM_001004416.3:c.1260T>C

Variant summary

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

The ENST00000408910.7(UMODL1):​c.1260T>C​(p.Ser420Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 1,612,020 control chromosomes in the GnomAD database, including 237,068 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 0.52 (20848 hom., cov: 32)
  • Exomes 𝑓: 0.54 (216220 hom.)
• Consequence: UMODL1 ENST00000408910.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.448
• Publications: 22 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]

UMODL1-AS1 (HGNC:23821): (UMODL1 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=0.448 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000408910.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UMODL1	NM_001004416.3	MANE Select	c.1260T>C	p.Ser420Ser	synonymous	Exon 8 of 23	NP_001004416.3
	UMODL1	NM_173568.4		c.1260T>C	p.Ser420Ser	synonymous	Exon 8 of 22	NP_775839.4
	UMODL1	NM_001199527.3		c.1044T>C	p.Ser348Ser	synonymous	Exon 8 of 22	NP_001186456.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UMODL1	ENST00000408910.7	TSL:1 MANE Select	c.1260T>C	p.Ser420Ser	synonymous	Exon 8 of 23	ENSP00000386147.2
	UMODL1	ENST00000408989.6	TSL:1	c.1260T>C	p.Ser420Ser	synonymous	Exon 8 of 22	ENSP00000386126.2
	UMODL1	ENST00000400427.5	TSL:1	c.1044T>C	p.Ser348Ser	synonymous	Exon 8 of 22	ENSP00000383279.1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79319 AN: 151910 Hom.: 20811 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.510

GnomAD2 exomes AF: 0.555 AC: 138340 AN: 249056 AF XY: 0.552

Gnomad AFR exome AF: 0.461

Gnomad AMR exome AF: 0.668

Gnomad ASJ exome AF: 0.540

Gnomad EAS exome AF: 0.579

Gnomad FIN exome AF: 0.542

Gnomad NFE exome AF: 0.536

Gnomad OTH exome AF: 0.561

GnomAD4 exome AF: 0.543 AC: 793204 AN: 1459994 Hom.: 216220 Cov.: 38 AF XY: 0.543 AC XY: 394351 AN XY: 726240

African (AFR) AF: 0.457 AC: 15288 AN: 33440

American (AMR) AF: 0.661 AC: 29506 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 14016 AN: 26090

East Asian (EAS) AF: 0.601 AC: 23828 AN: 39662

South Asian (SAS) AF: 0.556 AC: 47854 AN: 86064

European-Finnish (FIN) AF: 0.541 AC: 28839 AN: 53280

Middle Eastern (MID) AF: 0.571 AC: 3290 AN: 5766

European-Non Finnish (NFE) AF: 0.539 AC: 598377 AN: 1110752

Other (OTH) AF: 0.534 AC: 32206 AN: 60316

GnomAD4 genome AF: 0.522 AC: 79407 AN: 152026 Hom.: 20848 Cov.: 32 AF XY: 0.524 AC XY: 38912 AN XY: 74280

African (AFR) AF: 0.462 AC: 19143 AN: 41434

American (AMR) AF: 0.584 AC: 8933 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1845 AN: 3472

East Asian (EAS) AF: 0.568 AC: 2940 AN: 5174

South Asian (SAS) AF: 0.565 AC: 2721 AN: 4816

European-Finnish (FIN) AF: 0.535 AC: 5652 AN: 10558

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.535 AC: 36335 AN: 67976

Other (OTH) AF: 0.515 AC: 1086 AN: 2110

Alfa AF: 0.535 Hom.: 81392

Bravo AF: 0.525

Asia WGS AF: 0.554 AC: 1925 AN: 3478

EpiCase AF: 0.532

EpiControl AF: 0.541

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.4
DANN	Benign	0.50
PhyloP100		0.45
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: rs220109; hg19: chr21-43522349; COSMIC: COSV61159582;