12-100051137-G-A

Variant names:

• chr12-100051137-G-A
• rs768557331
• NM_015054.2:c.3509C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015054.2(BLTP3B):​c.3509C>T​(p.Thr1170Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. T1170S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BLTP3B NM_015054.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.16
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04742545).

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.3509C>T	p.Thr1170Ile	missense	Exon 16 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.3509C>T	p.Thr1170Ile	missense	Exon 16 of 21	ENSP00000279907.7	A0JNW5-1
	BLTP3B	ENST00000545232.6	TSL:1	c.2459C>T	p.Thr820Ile	missense	Exon 10 of 15	ENSP00000444824.2	A0A0C4DGH6
	BLTP3B	ENST00000949295.1		c.3509C>T	p.Thr1170Ile	missense	Exon 16 of 21	ENSP00000619354.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251344 AF XY: 0.00000736

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461796 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727190

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111970

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.096
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		2.2
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.037
Sift	Benign	0.13	T
Sift4G	Benign	0.11	T
Polyphen		0.015	B
Vest4		0.050
MutPred		0.15		Gain of catalytic residue at P1172 (P = 0.0262)
MVP		0.043
MPC		0.13
ClinPred		0.30	T
GERP RS		4.1
Varity_R		0.085
gMVP		0.16
Mutation Taster		=90/10	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

dbSNP: rs768557331; hg19: chr12-100444915;