chr2-241236626-C-G

Variant names:

• chr2-241236626-C-G
• rs557925333
• NM_005336.6:c.2893G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005336.6(HDLBP):​c.2893G>C​(p.Glu965Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E965K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: HDLBP NM_005336.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.32
• Publications: 1 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3174283).

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.2893G>C	p.Glu965Gln	missense	Exon 21 of 28	NP_005327.1	A0A024R4E5
	HDLBP	NM_001320965.3		c.2893G>C	p.Glu965Gln	missense	Exon 21 of 28	NP_001307894.1	Q00341-1
	HDLBP	NM_001320966.3		c.2893G>C	p.Glu965Gln	missense	Exon 21 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.2893G>C	p.Glu965Gln	missense	Exon 21 of 28	ENSP00000312042.4	Q00341-1
	HDLBP	ENST00000391975.5	TSL:1	c.2893G>C	p.Glu965Gln	missense	Exon 21 of 28	ENSP00000375836.1	Q00341-1
	HDLBP	ENST00000875612.1		c.2893G>C	p.Glu965Gln	missense	Exon 21 of 28	ENSP00000545671.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.59	T
PhyloP100		7.3
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.098
Sift	Benign	0.46	T
Sift4G	Benign	0.32	T
Vest4		0.52
MutPred		0.44		Loss of disorder (P = 0.107)
MVP		0.17
MPC		0.84
ClinPred		0.71	D
GERP RS		5.7
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
gMVP		0.53
Mutation Taster		=70/30	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

dbSNP: rs557925333; hg19: chr2-242176041;