rs1428837527

Variant names:

• chr10-103277269-G-A
• rs1428837527
• NM_032727.4:c.58G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-103277269-G-A
• chr10-103277269-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_032727.4(INA):​c.58G>A​(p.Gly20Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: INA NM_032727.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.03

Genes affected

INA (HGNC:6057): (internexin neuronal intermediate filament protein alpha) Neurofilaments are type IV intermediate filament heteropolymers composed of light, medium, and heavy chains. Neurofilaments comprise the axoskeleton and they functionally maintain the neuronal caliber. They may also play a role in intracellular transport to axons and dendrites. This gene is a member of the intermediate filament family and is involved in the morphogenesis of neurons. [provided by RefSeq, Jun 2009]

NT5C2 (HGNC:8022): (5'-nucleotidase, cytosolic II) This gene encodes a hydrolase that serves as an important role in cellular purine metabolism by acting primarily on inosine 5'-monophosphate and other purine nucleotides. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.94

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INA	NM_032727.4	c.58G>A	p.Gly20Arg	missense_variant	Exon 1 of 3	ENST00000369849.9	NP_116116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INA	ENST00000369849.9	c.58G>A	p.Gly20Arg	missense_variant	Exon 1 of 3	1	NM_032727.4	ENSP00000358865.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000139 AC: 2 AN: 1442076 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 717644

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.81	D
Eigen	Benign	0.14
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.95	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	0.032	D
MutationAssessor	Benign	1.6	L
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.3	D
REVEL	Pathogenic	0.68
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.14	T
Polyphen		0.70	P
Vest4		0.72
MutPred		0.79		Gain of methylation at G20 (P = 0.0168);
MVP		0.94
MPC		1.4
ClinPred		0.97	D
GERP RS		3.6
Varity_R		0.63
gMVP		0.65

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: rs1428837527; hg19: chr10-105037026;