10-103278010-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_032727.4(INA):​c.799G>A​(p.Glu267Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

INA
NM_032727.4 missense

Scores

13
4
2

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 10.0
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.916

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
INANM_032727.4 linkuse as main transcriptc.799G>A p.Glu267Lys missense_variant 1/3 ENST00000369849.9 NP_116116.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
INAENST00000369849.9 linkuse as main transcriptc.799G>A p.Glu267Lys missense_variant 1/31 NM_032727.4 ENSP00000358865 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

High myopia Uncertain:1
Uncertain significance, no assertion criteria providedresearchInstitute of Human Genetics, Polish Academy of SciencesDec 17, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.93
BayesDel_addAF
Pathogenic
0.32
D
BayesDel_noAF
Pathogenic
0.22
CADD
Pathogenic
34
DANN
Pathogenic
1.0
DEOGEN2
Pathogenic
0.90
D
Eigen
Pathogenic
0.89
Eigen_PC
Pathogenic
0.81
FATHMM_MKL
Benign
0.65
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Pathogenic
0.33
D
MetaRNN
Pathogenic
0.92
D
MetaSVM
Pathogenic
1.0
D
MutationAssessor
Uncertain
2.9
M
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.85
D
PROVEAN
Uncertain
-3.2
D
REVEL
Pathogenic
0.87
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0080
D
Polyphen
0.99
D
Vest4
0.72
MutPred
0.73
Gain of MoRF binding (P = 0.0014);
MVP
1.0
MPC
2.2
ClinPred
0.99
D
GERP RS
4.4
Varity_R
0.93
gMVP
0.90

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1564713713; hg19: chr10-105037767; COSMIC: COSV100878702; API