12-100047547-C-T

Variant names:

• chr12-100047547-C-T
• rs2095816177
• NM_015054.2:c.4064G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015054.2(BLTP3B):​c.4064G>A​(p.Gly1355Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,457,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: BLTP3B NM_015054.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.32

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.865

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLTP3B	NM_015054.2	c.4064G>A	p.Gly1355Asp	missense_variant	Exon 19 of 21	ENST00000279907.12	NP_055869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLTP3B	ENST00000279907.12	c.4064G>A	p.Gly1355Asp	missense_variant	Exon 19 of 21	1	NM_015054.2	ENSP00000279907.7
BLTP3B	ENST00000545232.6	c.3014G>A	p.Gly1005Asp	missense_variant	Exon 13 of 15	1		ENSP00000444824.2
BLTP3B	ENST00000548712.5	c.344G>A	p.Gly115Asp	missense_variant	Exon 2 of 4	3		ENSP00000447809.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1457796 Hom.: 0 Cov.: 29 AF XY: 0.00000413 AC XY: 3 AN XY: 725526

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: 0.00000451

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4064G>A (p.G1355D) alteration is located in exon 19 (coding exon 19) of the UHRF1BP1L gene. This alteration results from a G to A substitution at nucleotide position 4064, causing the glycine (G) at amino acid position 1355 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	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Uncertain	0.062	D
MutationAssessor	Uncertain	2.7	M;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-5.4	D;D
REVEL	Pathogenic	0.73
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		1.0	D;.
Vest4		0.95
MutPred		0.57		Loss of sheet (P = 0.0817);.;
MVP		0.45
MPC		0.64
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.93
gMVP		0.82

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: rs2095816177; hg19: chr12-100441325;