NM_001033088.3:c.539C>G

Variant names:

• chr15-90271451-C-G
• rs1325536585
• NM_001033088.3:c.539C>G

Variant summary

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

The NM_001033088.3(NGRN):​c.539C>G​(p.Ala180Gly) 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. 14/22 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: NGRN NM_001033088.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0540
• Publications: 0 publications found

Genes affected

NGRN (HGNC:18077): (neugrin, neurite outgrowth associated) Enables rRNA binding activity. Involved in positive regulation of mitochondrial translation. Located in several cellular components, including intercellular bridge; mitotic spindle; and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000275674 (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=0.10759303).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033088.3. 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
	NGRN	NM_001033088.3	MANE Select	c.539C>G	p.Ala180Gly	missense	Exon 3 of 3	NP_001028260.2	Q9NPE2-2
	NGRN	NR_028052.1		n.1000C>G		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGRN	ENST00000379095.5	TSL:1 MANE Select	c.539C>G	p.Ala180Gly	missense	Exon 3 of 3	ENSP00000368389.4	Q9NPE2-2
	ENSG00000275674	ENST00000622269.1	TSL:3	c.80+5053C>G		intron	N/A	ENSP00000479373.1	A0A087WVE0
	NGRN	ENST00000331497.3	TSL:1	n.1004C>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.092
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.054
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.088
Sift	Benign	0.28	T
Sift4G	Benign	0.076	T
Polyphen		0.89	P
Vest4		0.072
MutPred		0.45		Gain of relative solvent accessibility (P = 0.0098)
MVP		0.28
MPC		0.25
ClinPred		0.23	T
GERP RS		-2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.15

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: rs1325536585; hg19: chr15-90814683;