12-100057609-T-G

Variant names:

• chr12-100057609-T-G
• rs117457255
• NM_015054.2:c.3386A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015054.2(BLTP3B):​c.3386A>C​(p.Glu1129Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,458,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: BLTP3B NM_015054.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.36

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34545475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLTP3B	NM_015054.2	c.3386A>C	p.Glu1129Ala	missense_variant	Exon 15 of 21	ENST00000279907.12	NP_055869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLTP3B	ENST00000279907.12	c.3386A>C	p.Glu1129Ala	missense_variant	Exon 15 of 21	1	NM_015054.2	ENSP00000279907.7
BLTP3B	ENST00000545232.6	c.2336A>C	p.Glu779Ala	missense_variant	Exon 9 of 15	1		ENSP00000444824.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458966 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725672

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0033	T;T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.19
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.024	D;D
Polyphen		0.92	P;.
Vest4		0.64
MutPred		0.16		Gain of helix (P = 0.132);.;
MVP		0.093
MPC		0.54
ClinPred		0.94	D
GERP RS		5.7
Varity_R		0.39
gMVP		0.43

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: rs117457255; hg19: chr12-100451387;