rs368813038

Variant names:

• chr6-30689397-C-G
• rs368813038
• NM_001384369.1:c.386G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-30689397-C-G
• chr6-30689397-C-T

Variant summary

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

The NM_001384369.1(NRM):​c.386G>C​(p.Arg129Pro) 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. 16/22 in silico tools predict 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. R129Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NRM NM_001384369.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.919
• Publications: 0 publications found

Genes affected

NRM (HGNC:8003): (nurim) The protein encoded by this gene contains transmembrane domains and resides within the inner nuclear membrane, where it is tightly associated with the nucleus. This protein shares homology with isoprenylcysteine carboxymethyltransferase enzymes. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

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=0.24249884).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384369.1. 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
	NRM	NM_001384369.1	MANE Select	c.386G>C	p.Arg129Pro	missense	Exon 3 of 4	NP_001371298.1	Q8IXM6-1
	NRM	NM_001270707.2		c.404G>C	p.Arg135Pro	missense	Exon 3 of 4	NP_001257636.1
	NRM	NM_007243.3		c.386G>C	p.Arg129Pro	missense	Exon 4 of 5	NP_009174.1	A0A1U9X845

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRM	ENST00000376421.7	TSL:1 MANE Select	c.386G>C	p.Arg129Pro	missense	Exon 3 of 4	ENSP00000365603.5	Q8IXM6-1
	NRM	ENST00000376420.9	TSL:1	c.331-455G>C		intron	N/A	ENSP00000365602.5	Q8IXM6-2
	NRM	ENST00000474864.5	TSL:1	n.134-455G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	15
DANN	Benign	0.91
DEOGEN2	Benign	0.0095	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.27	N
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.92
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.18
Sift	Benign	0.072	T
Sift4G	Benign	0.17	T
Polyphen		0.94	P
Vest4		0.48
MutPred		0.35		Gain of glycosylation at R129 (P = 0.0146)
MVP		0.23
MPC		1.2
ClinPred		0.61	D
GERP RS		1.9
Varity_R		0.24
gMVP		0.73
Mutation Taster		=82/18	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: rs368813038; hg19: chr6-30657174;