12-100050177-G-A

Variant names:

• chr12-100050177-G-A
• rs771180318
• NM_015054.2:c.3709C>T

Variant summary

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

The NM_015054.2(BLTP3B):​c.3709C>T​(p.Arg1237Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000728 in 1,511,130 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000074 (0 hom.)
• Consequence: BLTP3B NM_015054.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.06
• Publications: 2 publications found

Genes affected

BLTP3B (HGNC:29102): (bridge-like lipid transfer protein family member 3B) Enables GARP complex binding activity and protein homodimerization activity. Located in cytosol and early endosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015054.2. 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
	BLTP3B	NM_015054.2	MANE Select	c.3709C>T	p.Arg1237Cys	missense	Exon 17 of 21	NP_055869.1	A0JNW5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLTP3B	ENST00000279907.12	TSL:1 MANE Select	c.3709C>T	p.Arg1237Cys	missense	Exon 17 of 21	ENSP00000279907.7	A0JNW5-1
	BLTP3B	ENST00000545232.6	TSL:1	c.2659C>T	p.Arg887Cys	missense	Exon 11 of 15	ENSP00000444824.2	A0A0C4DGH6
	BLTP3B	ENST00000949295.1		c.3709C>T	p.Arg1237Cys	missense	Exon 17 of 21	ENSP00000619354.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151908 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000240 AC: 4 AN: 166348 AF XY: 0.0000328

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: 0.0000549

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000736 AC: 10 AN: 1359222 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 9 AN XY: 673090

African (AFR) AF: 0.00 AC: 0 AN: 28886

American (AMR) AF: 0.00 AC: 0 AN: 24620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22302

East Asian (EAS) AF: 0.00 AC: 0 AN: 36656

South Asian (SAS) AF: 0.0000730 AC: 5 AN: 68514

European-Finnish (FIN) AF: 0.0000201 AC: 1 AN: 49672

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5384

European-Non Finnish (NFE) AF: 0.00000375 AC: 4 AN: 1067778

Other (OTH) AF: 0.00 AC: 0 AN: 55410

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151908 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74198

African (AFR) AF: 0.00 AC: 0 AN: 41380

American (AMR) AF: 0.0000656 AC: 1 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67972

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000604

ExAC AF: 0.00000825 AC: 1

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	0.14
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.056	T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.1
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.27
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.85
MutPred		0.39		Loss of sheet (P = 0.0181)
MVP		0.13
MPC		0.65
ClinPred		0.89	D
GERP RS		5.1
Varity_R		0.23
gMVP		0.61
Mutation Taster		=48/52	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs771180318; hg19: chr12-100443955; COSMIC: COSV54435931; COSMIC: COSV54435931;