10-103277368-G-C

Variant names:

• chr10-103277368-G-C
• NM_032727.4:c.157G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032727.4(INA):​c.157G>C​(p.Ala53Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,414,418 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: INA NM_032727.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INA	NM_032727.4	c.157G>C	p.Ala53Pro	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.157G>C	p.Ala53Pro	missense_variant	Exon 1 of 3	1	NM_032727.4	ENSP00000358865.4
NT5C2	ENST00000676449.1	c.-239C>G		5_prime_UTR_variant	Exon 1 of 18			ENSP00000502801.1
NT5C2	ENST00000675326.1	c.-383C>G		upstream_gene_variant				ENSP00000502205.1
NT5C2	ENST00000676428.1	c.-332C>G		upstream_gene_variant				ENSP00000501689.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.07e-7 AC: 1 AN: 1414418 Hom.: 0 Cov.: 32 AF XY: 0.00000142 AC XY: 1 AN XY: 702596

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: 9.13e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	0.0058	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.093
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.57	T
M_CAP	Pathogenic	0.96	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Benign	1.4	L
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.34	N
REVEL	Uncertain	0.36
Sift	Benign	0.15	T
Sift4G	Benign	0.30	T
Polyphen		0.97	D
Vest4		0.20
MutPred		0.58		Gain of catalytic residue at A53 (P = 0.0169);
MVP		0.95
MPC		1.2
ClinPred		0.32	T
GERP RS		1.7
Varity_R		0.083
gMVP		0.60

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: chr10-105037125;