6-30689361-C-A

Variant names:

• chr6-30689361-C-A
• rs775206079
• NM_001384369.1:c.422G>T

Variant summary

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

The NM_001384369.1(NRM):​c.422G>T​(p.Cys141Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000289 in 1,559,258 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: NRM NM_001384369.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.73
• 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 2 ACMG points.

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

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.422G>T	p.Cys141Phe	missense	Exon 3 of 4	NP_001371298.1	Q8IXM6-1
	NRM	NM_001270707.2		c.440G>T	p.Cys147Phe	missense	Exon 3 of 4	NP_001257636.1
	NRM	NM_007243.3		c.422G>T	p.Cys141Phe	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.422G>T	p.Cys141Phe	missense	Exon 3 of 4	ENSP00000365603.5	Q8IXM6-1
	NRM	ENST00000376420.9	TSL:1	c.331-419G>T		intron	N/A	ENSP00000365602.5	Q8IXM6-2
	NRM	ENST00000474864.5	TSL:1	n.134-419G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000598 AC: 1 AN: 167212 AF XY: 0.0000113

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000149

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000313 AC: 44 AN: 1407110 Hom.: 0 Cov.: 33 AF XY: 0.0000331 AC XY: 23 AN XY: 694916

African (AFR) AF: 0.00 AC: 0 AN: 31976

American (AMR) AF: 0.00 AC: 0 AN: 36578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25224

East Asian (EAS) AF: 0.00 AC: 0 AN: 36414

South Asian (SAS) AF: 0.00 AC: 0 AN: 79698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5668

European-Non Finnish (NFE) AF: 0.0000406 AC: 44 AN: 1083280

Other (OTH) AF: 0.00 AC: 0 AN: 58340

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152148 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74324

African (AFR) AF: 0.00 AC: 0 AN: 41416

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

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	Pathogenic	0.71
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0074	T
Eigen	Benign	0.025
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		3.7
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	0.65	N
REVEL	Benign	0.18
Sift	Benign	0.26	T
Sift4G	Benign	0.50	T
Polyphen		0.82	P
Vest4		0.79
MutPred		0.35		Loss of helix (P = 0.2271)
MVP		0.49
MPC		1.5
ClinPred		0.65	D
GERP RS		3.8
Varity_R		0.46
gMVP		0.78
Mutation Taster		=55/45	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: rs775206079; hg19: chr6-30657138;