Genetic Variant NM_015136.3:c.610T>C (chr3-52503025-T-C) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_015136.3(STAB1):c.610T>C(p.Cys204Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

STAB1
NM_015136.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.22

Publications

0 publications found

Variant links:

Genes affected

STAB1 (HGNC:18628): (stabilin 1) This gene encodes a large, transmembrane receptor protein which may function in angiogenesis, lymphocyte homing, cell adhesion, or receptor scavenging. The protein contains 7 fasciclin, 16 epidermal growth factor (EGF)-like, and 2 laminin-type EGF-like domains as well as a C-type lectin-like hyaluronan-binding Link module. The protein is primarily expressed on sinusoidal endothelial cells of liver, spleen, and lymph node. The receptor has been shown to endocytose ligands such as low density lipoprotein, Gram-positive and Gram-negative bacteria, and advanced glycosylation end products. Supporting its possible role as a scavenger receptor, the protein rapidly cycles between the plasma membrane and early endosomes. [provided by RefSeq, Jul 2008]

STAB1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.957

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015136.3. 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
	STAB1	NM_015136.3	MANE Select	c.610T>C	p.Cys204Arg	missense	Exon 7 of 69	NP_055951.2	Q9NY15-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STAB1	ENST00000321725.10	TSL:1 MANE Select	c.610T>C	p.Cys204Arg	missense	Exon 7 of 69	ENSP00000312946.6	Q9NY15-1
STAB1	ENST00000481607.1	TSL:1	n.665T>C		non_coding_transcript_exon	Exon 7 of 21
STAB1	ENST00000899926.1		c.610T>C	p.Cys204Arg	missense	Exon 7 of 69	ENSP00000569985.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000437

AC:

AN:

228606

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000972

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1446600

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718052

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33244

American (AMR)

AF:

0.00

AC:

AN:

43260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25766

East Asian (EAS)

AF:

0.00

AC:

AN:

39192

South Asian (SAS)

AF:

0.00

AC:

AN:

83672

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50996

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5106

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1105548

Other (OTH)

AF:

0.00

AC:

AN:

59816

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.72

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.67

M_CAP

Benign

0.054

MetaRNN

Pathogenic

0.96

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.2

PhyloP100

3.2

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-9.9

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.97

MutPred

0.70

Gain of phosphorylation at T208 (P = 0.2102)

MVP

0.59

MPC

1.1

ClinPred

1.0

GERP RS

5.1

Varity_R

0.95

gMVP

1.0

Mutation Taster

=72/28

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over