chr3-52503049-G-T

Variant names:

• chr3-52503049-G-T
• rs529062376
• NM_015136.3:c.634G>T

Variant summary

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

The NM_015136.3(STAB1):​c.634G>T​(p.Ala212Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,451,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: STAB1 NM_015136.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.680

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]

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=0.07289982).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAB1	NM_015136.3	c.634G>T	p.Ala212Ser	missense_variant	Exon 7 of 69	ENST00000321725.10	NP_055951.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAB1	ENST00000321725.10	c.634G>T	p.Ala212Ser	missense_variant	Exon 7 of 69	1	NM_015136.3	ENSP00000312946.6
STAB1	ENST00000481607.1	n.689G>T		non_coding_transcript_exon_variant	Exon 7 of 21	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1451404 Hom.: 0 Cov.: 33 AF XY: 0.00000139 AC XY: 1 AN XY: 721034

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.634G>T (p.A212S) alteration is located in exon 7 (coding exon 7) of the STAB1 gene. This alteration results from a G to T substitution at nucleotide position 634, causing the alanine (A) at amino acid position 212 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	2.4
DANN	Benign	0.94
DEOGEN2	Benign	0.064	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.027
Sift	Benign	0.58	T
Sift4G	Benign	0.29	T
Polyphen		0.17	B
Vest4		0.29
MutPred		0.20		Gain of glycosylation at A212 (P = 0.0452);
MVP		0.38
MPC		0.23
ClinPred		0.11	T
GERP RS		3.2
Varity_R		0.052
gMVP		0.45

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: rs529062376; hg19: chr3-52537065;