10-103277977-G-T

Position:

• chr10-103277977-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032727.4(INA):​c.766G>T​(p.Val256Leu) 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 benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: INA NM_032727.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.17

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3004849).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INA	NM_032727.4	c.766G>T	p.Val256Leu	missense_variant	1/3	ENST00000369849.9	NP_116116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INA	ENST00000369849.9	c.766G>T	p.Val256Leu	missense_variant	1/3	1	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: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2022

The c.766G>T (p.V256L) alteration is located in exon 1 (coding exon 1) of the INA gene. This alteration results from a G to T substitution at nucleotide position 766, causing the valine (V) at amino acid position 256 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.0061	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.095
Eigen_PC	Benign	0.054
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.30	T
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	0.94	D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.26
Sift	Benign	0.099	T
Sift4G	Benign	0.21	T
Polyphen		0.63	P
Vest4		0.20
MutPred		0.50		Loss of methylation at K258 (P = 0.1414);
MVP		0.95
MPC		1.0
ClinPred		0.68	D
GERP RS		4.3
Varity_R		0.10
gMVP		0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-105037734;