12-100050177-G-T

Variant names:

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

Variant summary

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

The NM_015054.2(BLTP3B):​c.3709C>A​(p.Arg1237Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000515 in 1,359,224 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1237C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000051 (0 hom.)
• Consequence: BLTP3B NM_015054.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.06
• Publications: 0 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>A	p.Arg1237Ser	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>A	p.Arg1237Ser	missense	Exon 17 of 21	ENSP00000279907.7	A0JNW5-1
	BLTP3B	ENST00000545232.6	TSL:1	c.2659C>A	p.Arg887Ser	missense	Exon 11 of 15	ENSP00000444824.2	A0A0C4DGH6
	BLTP3B	ENST00000949295.1		c.3709C>A	p.Arg1237Ser	missense	Exon 17 of 21	ENSP00000619354.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000515 AC: 7 AN: 1359224 Hom.: 0 Cov.: 32 AF XY: 0.00000446 AC XY: 3 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: 0.0000146 AC: 1 AN: 68514

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49674

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

European-Non Finnish (NFE) AF: 0.00000562 AC: 6 AN: 1067778

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0036	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.1
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.17
Sift	Benign	0.16	T
Sift4G	Uncertain	0.033	D
Polyphen		0.99	D
Vest4		0.86
MutPred		0.36		Gain of disorder (P = 0.0695)
MVP		0.082
MPC		0.59
ClinPred		0.97	D
GERP RS		5.1
Varity_R		0.30
gMVP		0.68
Mutation Taster		=46/54	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;