NM_177551.4:c.960G>T

Variant names:

• chr12-122702324-C-A
• rs1228597849
• NM_177551.4:c.960G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_177551.4(HCAR2):​c.960G>T​(p.Glu320Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HCAR2 NM_177551.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.998
• Publications: 0 publications found

Genes affected

HCAR2 (HGNC:24827): (hydroxycarboxylic acid receptor 2) Predicted to enable nicotinic acid receptor activity. Involved in neutrophil apoptotic process and positive regulation of neutrophil apoptotic process. Located in cell junction and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000256249 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07307038).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177551.4. 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
	HCAR2	NM_177551.4	MANE Select	c.960G>T	p.Glu320Asp	missense	Exon 1 of 1	NP_808219.1	Q8TDS4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCAR2	ENST00000328880.6	TSL:6 MANE Select	c.960G>T	p.Glu320Asp	missense	Exon 1 of 1	ENSP00000375066.2	Q8TDS4
	ENSG00000256249	ENST00000543611.1	TSL:4	n.401+994C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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	0.071
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.27
DANN	Uncertain	0.97
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		-1.0
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.042
Sift	Benign	0.42	T
Sift4G	Benign	0.21	T
Polyphen		0.16	B
Vest4		0.13
MutPred		0.28		Loss of ubiquitination at K316 (P = 0.0952)
MVP		0.27
MPC		0.66
ClinPred		0.23	T
GERP RS		2.7
Varity_R		0.037
gMVP		0.21
Mutation Taster		=92/8	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: rs1228597849; hg19: chr12-123186871;