NM_005336.6:c.3277G>A

Variant names:

• chr2-241233831-C-T
• NM_005336.6:c.3277G>A

Variant summary

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

The NM_005336.6(HDLBP):​c.3277G>A​(p.Asp1093Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HDLBP NM_005336.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.80
• Publications: 0 publications found

Genes affected

HDLBP (HGNC:4857): (high density lipoprotein binding protein) The protein encoded by this gene binds high density lipoprotein (HDL) and may function to regulate excess cholesterol levels in cells. The encoded protein also binds RNA and can induce heterochromatin formation. [provided by RefSeq, Mar 2016]

ANO7 (HGNC:31677): (anoctamin 7) This prostate-specific gene encodes a cytoplasmic protein, as well as a polytopic membrane protein which may serve as a target in prostate cancer diagnosis and immunotherapy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005336.6. 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
	HDLBP	NM_005336.6	MANE Select	c.3277G>A	p.Asp1093Asn	missense	Exon 24 of 28	NP_005327.1	A0A024R4E5
	HDLBP	NM_001320965.3		c.3277G>A	p.Asp1093Asn	missense	Exon 24 of 28	NP_001307894.1	Q00341-1
	HDLBP	NM_001320966.3		c.3277G>A	p.Asp1093Asn	missense	Exon 24 of 28	NP_001307895.1	Q00341-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDLBP	ENST00000310931.10	TSL:1 MANE Select	c.3277G>A	p.Asp1093Asn	missense	Exon 24 of 28	ENSP00000312042.4	Q00341-1
	HDLBP	ENST00000391975.5	TSL:1	c.3277G>A	p.Asp1093Asn	missense	Exon 24 of 28	ENSP00000375836.1	Q00341-1
	HDLBP	ENST00000875612.1		c.3391G>A	p.Asp1131Asn	missense	Exon 24 of 28	ENSP00000545671.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461854 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727222

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	22
DANN	Uncertain	1.0
Eigen	Benign	0.0059
Eigen_PC	Benign	-0.062
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.1	T
PhyloP100		7.8
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.17
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.082	T
Vest4		0.56
MutPred		0.29		Gain of methylation at K1091 (P = 0.1398)
MVP		0.32
MPC		1.0
ClinPred		0.85	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
gMVP		0.82
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

hg19: chr2-242173246;