rs1916341

Variant names:

• chr10-73911404-G-A
• rs1916341
• NM_002658.6:c.-31-121G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-73911404-G-A
• chr10-73911404-G-C
• chr10-73911404-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002658.6(PLAU):​c.-31-121G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000111 in 900,164 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: 33)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: PLAU NM_002658.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266
• Publications: 0 publications found

Genes affected

PLAU (HGNC:9052): (plasminogen activator, urokinase) This gene encodes a secreted serine protease that converts plasminogen to plasmin. The encoded preproprotein is proteolytically processed to generate A and B polypeptide chains. These chains associate via a single disulfide bond to form the catalytically inactive high molecular weight urokinase-type plasminogen activator (HMW-uPA). HMW-uPA can be further processed into the catalytically active low molecular weight urokinase-type plasminogen activator (LMW-uPA). This low molecular weight form does not bind to the urokinase-type plasminogen activator receptor. Mutations in this gene may be associated with Quebec platelet disorder and late-onset Alzheimer's disease. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

C10orf55 (HGNC:31008): (chromosome 10 putative open reading frame 55) Enables identical protein binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002658.6. 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
	PLAU	NM_002658.6	MANE Select	c.-31-121G>A		intron	N/A	NP_002649.2
	PLAU	NM_001441154.1		c.-31-121G>A		intron	N/A	NP_001428083.1
	PLAU	NM_001441155.1		c.-31-121G>A		intron	N/A	NP_001428084.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAU	ENST00000372764.4	TSL:1 MANE Select	c.-31-121G>A		intron	N/A	ENSP00000361850.3
	C10orf55	ENST00000409178.5	TSL:1	n.1078C>T		non_coding_transcript_exon	Exon 5 of 5
	PLAU	ENST00000894723.1		c.-152G>A		5_prime_UTR	Exon 1 of 10	ENSP00000564782.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000111 AC: 1 AN: 900164 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 462328

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22220

American (AMR) AF: 0.00 AC: 0 AN: 34870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21936

East Asian (EAS) AF: 0.00 AC: 0 AN: 33570

South Asian (SAS) AF: 0.00 AC: 0 AN: 68670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33184

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3132

European-Non Finnish (NFE) AF: 0.00000156 AC: 1 AN: 640892

Other (OTH) AF: 0.00 AC: 0 AN: 41690

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.9
DANN	Benign	0.75
PhyloP100		-0.27
PromoterAI		0.024	Neutral

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: rs1916341; hg19: chr10-75671162;