6-30690078-A-G

Position:

• chr6-30690078-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001384369.1(NRM):​c.299T>C​(p.Leu100Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NRM NM_001384369.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.91

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]

NRM (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRM	NM_001384369.1	c.299T>C	p.Leu100Pro	missense_variant	2/4	ENST00000376421.7	NP_001371298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRM	ENST00000376421.7	c.299T>C	p.Leu100Pro	missense_variant	2/4	1	NM_001384369.1	ENSP00000365603.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2024

The c.299T>C (p.L100P) alteration is located in exon 2 (coding exon 2) of the NRM gene. This alteration results from a T to C substitution at nucleotide position 299, causing the leucine (L) at amino acid position 100 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	.;T;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Benign	0.72	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.69	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L;L
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.9	D;D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.057	T;D;D
Polyphen		0.97	.;D;D
Vest4		0.78
MutPred		0.55		Loss of stability (P = 0.0251);Loss of stability (P = 0.0251);Loss of stability (P = 0.0251);
MVP		0.66
MPC		1.5
ClinPred		0.97	D
GERP RS		4.6
Varity_R		0.55
gMVP		0.84

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-30657855;