NM_014680.5:c.5954T>A

Variant names:

• chr17-28616956-A-T
• NM_014680.5:c.5954T>A

Variant summary

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

The NM_014680.5(BLTP2):​c.5954T>A​(p.Leu1985Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BLTP2 NM_014680.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.73

Genes affected

BLTP2 (HGNC:28960): (bridge-like lipid transfer protein family member 2) This gene was initially characterized in human as having high expression levels in breast carcinomas and breast cancer cell lines. This gene also has increased expression in prostrate cancer cells relative to normal prostrate tissues. Expression of this gene is negatively regulated by direct binding of the microRNA miR-195 to its 3' UTR. miR-195 has been shown to modulate the invasiveness of prostrate cancer cells and xenograft metastases by downgrading expression of this gene. In mouse, the protein encoded by this gene was identified as an antigen on acute monocytic leukemia cells. In human, alternative splicing results in multiple transcript variants encoding distinct isoforms; some of these isoforms are predicted to contain an RNA pol II promoter FMP27 protein domain and a Golgi-body-localization APT1 domain. [provided by RefSeq, Apr 2017]

SPAG5-AS1 (HGNC:41140): (SPAG5 antisense RNA 1)

ACMG classification

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
BLTP2	NM_014680.5	c.5954T>A	p.Leu1985Gln	missense_variant	Exon 34 of 39	ENST00000528896.7	NP_055495.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLTP2	ENST00000528896.7	c.5954T>A	p.Leu1985Gln	missense_variant	Exon 34 of 39	1	NM_014680.5	ENSP00000436773.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461772 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727178

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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 Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0011	T;T;T
Eigen	Uncertain	0.63
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.60	D;D;D
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.76	N;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.24	N;N;.
REVEL	Benign	0.25
Sift	Benign	0.034	D;D;.
Sift4G	Uncertain	0.027	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.72
MutPred		0.61		Gain of disorder (P = 0.0123);.;.;
MVP		0.50
MPC		1.4
ClinPred		0.80	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-26943974;