NM_015054.2:c.4325T>C

Variant names:

• chr12-100037706-A-G
• rs1158867828
• NM_015054.2:c.4325T>C

Variant summary

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

The NM_015054.2(BLTP3B):​c.4325T>C​(p.Met1442Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,459,158 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M1442K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: BLTP3B NM_015054.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.74
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1228511).

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.4325T>C	p.Met1442Thr	missense	Exon 21 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.4325T>C	p.Met1442Thr	missense	Exon 21 of 21	ENSP00000279907.7	A0JNW5-1
	BLTP3B	ENST00000545232.6	TSL:1	c.3275T>C	p.Met1092Thr	missense	Exon 15 of 15	ENSP00000444824.2	A0A0C4DGH6
	BLTP3B	ENST00000949295.1		c.4226T>C	p.Met1409Thr	missense	Exon 21 of 21	ENSP00000619354.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459158 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725898

African (AFR) AF: 0.00 AC: 0 AN: 33318

American (AMR) AF: 0.00 AC: 0 AN: 43952

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39590

South Asian (SAS) AF: 0.00 AC: 0 AN: 85608

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111368

Other (OTH) AF: 0.00 AC: 0 AN: 60308

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0052	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.7
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.045
Sift	Benign	0.031	D
Sift4G	Benign	0.19	T
Polyphen		0.65	P
Vest4		0.34
MutPred		0.28		Gain of phosphorylation at M1442 (P = 0.0774)
MVP		0.043
MPC		0.14
ClinPred		0.61	D
GERP RS		4.5
Varity_R		0.14
gMVP		0.35
Mutation Taster		=80/20	polymorphism

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: rs1158867828; hg19: chr12-100431484;