15-90271432-C-T

Variant names:

• chr15-90271432-C-T
• rs11073922
• NM_001033088.3:c.520C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001033088.3(NGRN):​c.520C>T​(p.Leu174Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 1,613,948 control chromosomes in the GnomAD database, including 7,348 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.073 (553 hom., cov: 32)
  • Exomes 𝑓: 0.093 (6795 hom.)
• Consequence: NGRN NM_001033088.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.627
• Publications: 17 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022950768).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0968 is higher than 0.05.

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.520C>T	p.Leu174Phe	missense	Exon 3 of 3	NP_001028260.2
	NGRN	NR_028052.1		n.981C>T		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.520C>T	p.Leu174Phe	missense	Exon 3 of 3	ENSP00000368389.4
	ENSG00000275674	ENST00000622269.1	TSL:3	c.80+5034C>T		intron	N/A	ENSP00000479373.1
	NGRN	ENST00000331497.3	TSL:1	n.985C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0729 AC: 11092 AN: 152118 Hom.: 549 Cov.: 32

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0941

Gnomad ASJ AF: 0.0522

Gnomad EAS AF: 0.0386

Gnomad SAS AF: 0.0942

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0988

Gnomad OTH AF: 0.0836

GnomAD2 exomes AF: 0.0886 AC: 22236 AN: 250870 AF XY: 0.0913

Gnomad AFR exome AF: 0.0163

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.0603

Gnomad EAS exome AF: 0.0321

Gnomad FIN exome AF: 0.110

Gnomad NFE exome AF: 0.0981

Gnomad OTH exome AF: 0.0911

GnomAD4 exome AF: 0.0933 AC: 136446 AN: 1461712 Hom.: 6795 Cov.: 32 AF XY: 0.0939 AC XY: 68297 AN XY: 727142

African (AFR) AF: 0.0132 AC: 443 AN: 33472

American (AMR) AF: 0.103 AC: 4590 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0592 AC: 1548 AN: 26134

East Asian (EAS) AF: 0.0360 AC: 1431 AN: 39700

South Asian (SAS) AF: 0.102 AC: 8819 AN: 86254

European-Finnish (FIN) AF: 0.112 AC: 5973 AN: 53340

Middle Eastern (MID) AF: 0.0690 AC: 398 AN: 5764

European-Non Finnish (NFE) AF: 0.0973 AC: 108146 AN: 1111942

Other (OTH) AF: 0.0844 AC: 5098 AN: 60388

GnomAD4 genome AF: 0.0730 AC: 11106 AN: 152236 Hom.: 553 Cov.: 32 AF XY: 0.0725 AC XY: 5397 AN XY: 74428

African (AFR) AF: 0.0182 AC: 757 AN: 41552

American (AMR) AF: 0.0946 AC: 1444 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0522 AC: 181 AN: 3468

East Asian (EAS) AF: 0.0387 AC: 201 AN: 5190

South Asian (SAS) AF: 0.0947 AC: 457 AN: 4826

European-Finnish (FIN) AF: 0.103 AC: 1091 AN: 10588

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0988 AC: 6720 AN: 68020

Other (OTH) AF: 0.0836 AC: 177 AN: 2116

Alfa AF: 0.0823 Hom.: 766

Bravo AF: 0.0693

TwinsUK AF: 0.0909 AC: 337

ALSPAC AF: 0.0903 AC: 348

ESP6500AA AF: 0.0182 AC: 80

ESP6500EA AF: 0.0982 AC: 844

ExAC AF: 0.0877 AC: 10650

Asia WGS AF: 0.0590 AC: 203 AN: 3478

EpiCase AF: 0.0914

EpiControl AF: 0.0899

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.064
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.68	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.63
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.19
Sift	Uncertain	0.0070	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.056
MPC		0.46
ClinPred		0.023	T
GERP RS		3.5
Varity_R		0.17
gMVP		0.39
Mutation Taster		=89/11	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs11073922; hg19: chr15-90814664; COSMIC: COSV107385115; COSMIC: COSV107385115;