chr19-17405539-T-C

Variant names:

• chr19-17405539-T-C
• NM_004335.4:c.37A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004335.4(BST2):​c.37A>G​(p.Met13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BST2 NM_004335.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0870
• Publications: 0 publications found

Genes affected

BST2 (HGNC:1119): (bone marrow stromal cell antigen 2) Bone marrow stromal cells are involved in the growth and development of B-cells. The specific function of the protein encoded by the bone marrow stromal cell antigen 2 is undetermined; however, this protein may play a role in pre-B-cell growth and in rheumatoid arthritis. [provided by RefSeq, Jul 2008]

BISPR (HGNC:51290): (BST2 interferon stimulated positive regulator)

MVB12A (HGNC:25153): (multivesicular body subunit 12A) Enables lipid binding activity and ubiquitin binding activity. Involved in regulation of epidermal growth factor receptor signaling pathway; viral budding; and virus maturation. Located in several cellular components, including Golgi apparatus; centrosome; and nucleoplasm. Part of ESCRT I complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19864109).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004335.4. 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
	BST2	NM_004335.4	MANE Select	c.37A>G	p.Met13Val	missense	Exon 1 of 5	NP_004326.1	A0A024R7H5
	MVB12A	NM_001304547.2		c.-639T>C		upstream_gene	N/A	NP_001291476.1
	BISPR	NR_130765.1		n.-147T>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BST2	ENST00000252593.7	TSL:1 MANE Select	c.37A>G	p.Met13Val	missense	Exon 1 of 5	ENSP00000252593.6	Q10589-1
	BST2	ENST00000860181.1		c.37A>G	p.Met13Val	missense	Exon 1 of 4	ENSP00000530240.1
	BST2	ENST00000860182.1		c.37A>G	p.Met13Val	missense	Exon 1 of 5	ENSP00000530241.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	11
DANN	Benign	0.75
DEOGEN2	Benign	0.073	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.087
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.10
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.087	T
Polyphen		0.92	P
Vest4		0.24
MutPred		0.25		Loss of ubiquitination at K18 (P = 0.0637)
MVP		0.78
MPC		1.3
ClinPred		0.30	T
GERP RS		2.9
PromoterAI		0.031	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.86
gMVP		0.16
Mutation Taster		=98/2	polymorphism

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

hg19: chr19-17516348;