Genetic Variant BLTP3B:p.Thr1462Ala (chr12-100037647-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015054.2(BLTP3B):c.4384A>G(p.Thr1462Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000212 in 1,608,962 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

BLTP3B
NM_015054.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.671

Variant links:

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]

BLTP3B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.015911102).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLTP3B	NM_015054.2 link	c.4384A>G	p.Thr1462Ala	missense_variant	Exon 21 of 21	ENST00000279907.12	NP_055869.1	A0JNW5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BLTP3B	ENST00000279907.12 link	c.4384A>G	p.Thr1462Ala	missense_variant	Exon 21 of 21	1	NM_015054.2	ENSP00000279907.7	A0JNW5-1
BLTP3B	ENST00000545232.6 link	c.3334A>G	p.Thr1112Ala	missense_variant	Exon 15 of 15	1		ENSP00000444824.2	A0A0C4DGH6
BLTP3B	ENST00000548712.5 link	c.555+1949A>G		intron_variant	Intron 3 of 3	3		ENSP00000447809.1	H0YHT7

Frequencies

GnomAD3 genomes

AF:

0.000190

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000269

AC:

AN:

245162

Hom.:

AF XY:

0.000339

AC XY:

AN XY:

132678

show subpopulations

Gnomad AFR exome

AF:

0.0000629

Gnomad AMR exome

AF:

0.000122

Gnomad ASJ exome

AF:

0.000904

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000543

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000304

Gnomad OTH exome

AF:

0.000337

GnomAD4 exome

AF:

0.000214

AC:

312

AN:

1456718

Hom.:

Cov.:

AF XY:

0.000247

AC XY:

179

AN XY:

724616

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000183

Gnomad4 ASJ exome

AF:

0.000768

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000540

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000175

Gnomad4 OTH exome

AF:

0.000448

GnomAD4 genome

AF:

0.000190

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000332

Hom.:

Bravo

AF:

0.000162

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000296

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 03, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4384A>G (p.T1462A) alteration is located in exon 21 (coding exon 21) of the UHRF1BP1L gene. This alteration results from a A to G substitution at nucleotide position 4384, causing the threonine (T) at amino acid position 1462 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.0017

T;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.016

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;.

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.97

N;N

REVEL

Benign

0.056

Sift

Benign

0.36

T;T

Sift4G

Benign

0.33

T;T

Polyphen

0.0

B;.

Vest4

0.041

MVP

0.043

MPC

0.11

ClinPred

0.0094

GERP RS

0.076

Varity_R

0.067

gMVP

0.12

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over