rs199785374

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_032727.4(INA):c.5G>A(p.Ser2Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000545 in 1,578,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

INA
NM_032727.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.10

Publications

0 publications found

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]

INA links:

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]

NT5C2 Gene-Disease associations (from GenCC):

complex hereditary spastic paraplegia
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hereditary spastic paraplegia 45
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae)

NT5C2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 2.1276 (below the threshold of 3.09). Trascript score misZ: 0.35672 (below the threshold of 3.09).

BP4

Computational evidence support a benign effect (MetaRNN=0.37241417).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032727.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INA	NM_032727.4	MANE Select	c.5G>A	p.Ser2Asn	missense	Exon 1 of 3	NP_116116.1	Q16352

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
INA	ENST00000369849.9	TSL:1 MANE Select	c.5G>A	p.Ser2Asn	missense	Exon 1 of 3	ENSP00000358865.4	Q16352
INA	ENST00000912062.1		c.5G>A	p.Ser2Asn	missense	Exon 1 of 3	ENSP00000582121.1
NT5C2	ENST00000675326.1		c.-231C>T		5_prime_UTR	Exon 1 of 19	ENSP00000502205.1	P49902-1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000991

AC:

AN:

201862

AF XY:

0.000115

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000998

Gnomad ASJ exome

AF:

0.00165

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000335

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000533

AC:

AN:

1425960

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

709424

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29388

American (AMR)

AF:

0.000170

AC:

AN:

41212

Ashkenazi Jewish (ASJ)

AF:

0.00177

AC:

AN:

24924

East Asian (EAS)

AF:

0.00

AC:

AN:

34656

South Asian (SAS)

AF:

0.00

AC:

AN:

83394

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50156

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5508

European-Non Finnish (NFE)

AF:

0.0000182

AC:

AN:

1097840

Other (OTH)

AF:

0.0000849

AC:

AN:

58882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152120

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41452

American (AMR)

AF:

0.000262

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67988

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000249

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000587

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.46

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.47

M_CAP

Pathogenic

0.85

MetaRNN

Benign

0.37

MetaSVM

Uncertain

-0.028

MutationAssessor

Uncertain

2.2

PhyloP100

5.1

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.46

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0030

Polyphen

0.97

Vest4

0.25

MVP

0.93

MPC

2.1

ClinPred

0.27

GERP RS

3.8

PromoterAI

0.022

Neutral

(source)

Varity_R

0.68

gMVP

0.69

Mutation Taster

=57/43

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over