21-42102254-C-T

Variant names:

• chr21-42102254-C-T
• rs1309428866
• NM_001004416.3:c.1275C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001004416.3(UMODL1):​c.1275C>T​(p.Asp425Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,546 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UMODL1 NM_001004416.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.700
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=0.7 with no splicing effect.

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.1275C>T	p.Asp425Asp	synonymous	Exon 8 of 23	NP_001004416.3	Q5DID0-1
	UMODL1	NM_173568.4		c.1275C>T	p.Asp425Asp	synonymous	Exon 8 of 22	NP_775839.4
	UMODL1	NM_001199527.3		c.1059C>T	p.Asp353Asp	synonymous	Exon 8 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.1275C>T	p.Asp425Asp	synonymous	Exon 8 of 23	ENSP00000386147.2	Q5DID0-1
	UMODL1	ENST00000408989.6	TSL:1	c.1275C>T	p.Asp425Asp	synonymous	Exon 8 of 22	ENSP00000386126.2	Q5DID0-2
	UMODL1	ENST00000400427.5	TSL:1	c.1059C>T	p.Asp353Asp	synonymous	Exon 8 of 22	ENSP00000383279.1	Q5DID0-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460546 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726486

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111198

Other (OTH) AF: 0.00 AC: 0 AN: 60354

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.3
DANN	Benign	0.73
PhyloP100		0.70

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: rs1309428866; hg19: chr21-43522364;