rs189377046

Variant names:

• chr6-160537897-C-A
• rs189377046
• NM_005577.4:c.5800G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-160537897-C-A
• chr6-160537897-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005577.4(LPA):​c.5800G>T​(p.Ala1934Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict 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: 0.0000055 (0 hom.)
• Consequence: LPA NM_005577.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31

Genes affected

LPA (HGNC:6667): (lipoprotein(a)) The protein encoded by this gene is a serine proteinase that inhibits the activity of tissue-type plasminogen activator I. The encoded protein constitutes a substantial portion of lipoprotein(a) and is proteolytically cleaved, resulting in fragments that attach to atherosclerotic lesions and promote thrombogenesis. Elevated plasma levels of this protein are linked to atherosclerosis. Depending on the individual, the encoded protein contains 2-43 copies of kringle-type domains. The allele represented here contains 15 copies of the kringle-type repeats and corresponds to that found in the reference genome sequence. [provided by RefSeq, Dec 2009]

LOC124901454 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.115525186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4	c.5800G>T	p.Ala1934Ser	missense_variant	Exon 37 of 39	ENST00000316300.10	NP_005568.2
LOC124901454	XR_007059844.1	n.484-1620C>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10	c.5800G>T	p.Ala1934Ser	missense_variant	Exon 37 of 39	1	NM_005577.4	ENSP00000321334.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251366 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135876

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461850 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727228

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0000749

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	6.5
DANN	Benign	0.89
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.13	N
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.35	T
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.39	N
REVEL	Benign	0.24
Sift	Benign	0.52	T
Sift4G	Benign	0.29	T
Vest4		0.098
MVP		0.39
ClinPred		0.11	T
GERP RS		1.7
gMVP		0.23

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: rs189377046; hg19: chr6-160958929;