15-90271327-A-G

Variant names:

• chr15-90271327-A-G
• rs143871202
• NM_001033088.3:c.415A>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001033088.3(NGRN):​c.415A>G​(p.Lys139Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0012 in 1,614,108 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0024 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (31 hom.)
• Consequence: NGRN NM_001033088.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.35

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008569419).
• BP6: Variant 15-90271327-A-G is Benign according to our data. Variant chr15-90271327-A-G is described in ClinVar as [Benign]. Clinvar id is 784619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00242 (369/152294) while in subpopulation AMR AF= 0.0224 (342/15284). AF 95% confidence interval is 0.0204. There are 6 homozygotes in gnomad4. There are 216 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGRN	NM_001033088.3	c.415A>G	p.Lys139Glu	missense_variant	Exon 3 of 3	ENST00000379095.5	NP_001028260.2
NGRN	NR_028052.1	n.876A>G		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGRN	ENST00000379095.5	c.415A>G	p.Lys139Glu	missense_variant	Exon 3 of 3	1	NM_001033088.3	ENSP00000368389.4
ENSG00000275674	ENST00000622269.1	c.80+4929A>G		intron_variant	Intron 1 of 3	3		ENSP00000479373.1
ENSG00000261147	ENST00000561573.1	n.*2039A>G		non_coding_transcript_exon_variant	Exon 13 of 13	2		ENSP00000456615.1
ENSG00000261147	ENST00000561573.1	n.*2039A>G		3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000456615.1

Frequencies

GnomAD3 genomes AF: 0.00241 AC: 367 AN: 152176 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0223

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00525 AC: 1318 AN: 251120 Hom.: 26 AF XY: 0.00400 AC XY: 544 AN XY: 135868

Gnomad AFR exome AF: 0.000497

Gnomad AMR exome AF: 0.0372

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00343

GnomAD4 exome AF: 0.00107 AC: 1569 AN: 1461814 Hom.: 31 Cov.: 31 AF XY: 0.000927 AC XY: 674 AN XY: 727200

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.0332

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000216

Gnomad4 OTH exome AF: 0.000845

GnomAD4 genome AF: 0.00242 AC: 369 AN: 152294 Hom.: 6 Cov.: 32 AF XY: 0.00290 AC XY: 216 AN XY: 74460

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.0224

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.000195 Hom.: 0

Bravo AF: 0.00410

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00384 AC: 466

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 09, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.0086	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.29
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.33
MVP		0.85
MPC		0.52
ClinPred		0.044	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.39
gMVP		0.56

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

LitVar

Other links and lift over

dbSNP: rs143871202; hg19: chr15-90814559;