Genetic Variant BLTP3B:p.Asn1322Asp (chr12-100047951-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015054.2(BLTP3B):c.3964A>G(p.Asn1322Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000054 in 1,482,452 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

BLTP3B
NM_015054.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.14

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLTP3B	NM_015054.2 link	c.3964A>G	p.Asn1322Asp	missense_variant	Exon 18 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.3964A>G	p.Asn1322Asp	missense_variant	Exon 18 of 21	1	NM_015054.2	ENSP00000279907.7	A0JNW5-1
BLTP3B	ENST00000545232.6 link	c.2914A>G	p.Asn972Asp	missense_variant	Exon 12 of 15	1		ENSP00000444824.2	A0A0C4DGH6
BLTP3B	ENST00000548712.5 link	c.244A>G	p.Asn82Asp	missense_variant	Exon 1 of 4	3		ENSP00000447809.1	H0YHT7

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000814

AC:

AN:

122832

Hom.:

AF XY:

0.00

AC XY:

AN XY:

66240

show subpopulations

Gnomad AFR exome

AF:

0.000121

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000150

AC:

AN:

1330246

Hom.:

Cov.:

AF XY:

0.00000153

AC XY:

AN XY:

652576

show subpopulations

Gnomad4 AFR exome

AF:

0.0000700

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000453

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3964A>G (p.N1322D) alteration is located in exon 18 (coding exon 18) of the UHRF1BP1L gene. This alteration results from a A to G substitution at nucleotide position 3964, causing the asparagine (N) at amino acid position 1322 to be replaced by an aspartic acid (D). 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

0.15

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0046

T;T

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.81

T;D

M_CAP

Benign

0.0085

MetaRNN

Uncertain

0.47

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.14

Sift

Benign

0.13

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.74

P;.

Vest4

0.80

MutPred

0.30

Gain of ubiquitination at K1320 (P = 0.0371);.;

MVP

0.043

MPC

0.15

ClinPred

0.18

GERP RS

5.7

Varity_R

0.26

gMVP

0.54

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