6-30689176-G-T

Variant names:

• chr6-30689176-G-T
• rs2269704
• NM_001384369.1:c.507+100C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001384369.1(NRM):​c.507+100C>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NRM NM_001384369.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRM	NM_001384369.1	MANE Select	c.507+100C>A		intron	N/A	NP_001371298.1
	NRM	NM_001270707.2		c.525+100C>A		intron	N/A	NP_001257636.1
	NRM	NM_007243.3		c.507+100C>A		intron	N/A	NP_009174.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRM	ENST00000376421.7	TSL:1 MANE Select	c.507+100C>A		intron	N/A	ENSP00000365603.5
	NRM	ENST00000376420.9	TSL:1	c.331-234C>A		intron	N/A	ENSP00000365602.5
	NRM	ENST00000474864.5	TSL:1	n.134-234C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1103918 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 546054

African (AFR) AF: 0.00 AC: 0 AN: 24272

American (AMR) AF: 0.00 AC: 0 AN: 23236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18338

East Asian (EAS) AF: 0.00 AC: 0 AN: 34172

South Asian (SAS) AF: 0.00 AC: 0 AN: 60928

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4566

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 848712

Other (OTH) AF: 0.00 AC: 0 AN: 47472

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.49
DANN	Benign	0.49
PhyloP100		-0.43

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: rs2269704; hg19: chr6-30656953;