Genetic Variant ARV1:p.Thr95Pro (chr1-230988428-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_022786.3(ARV1):c.283A>C(p.Thr95Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000258 in 1,553,076 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ARV1
NM_022786.3 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 8.90

Publications

1 publications found

Variant links:

Genes affected

ARV1 (HGNC:29561): (ARV1 homolog, fatty acid homeostasis modulator) this gene encodes a transmembrane protein that contains a conserved zinc ribbon motif at the N- terminus. A similar protein in mouse is thought to function in fatty acid homeostasis. Mutations in this gene are associated with early infantile epileptic encephalopathy 38. [provided by RefSeq, Nov 2016]

ARV1 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 38
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ARV1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022786.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARV1	NM_022786.3	MANE Select	c.283A>C	p.Thr95Pro	missense	Exon 2 of 6	NP_073623.1	Q9H2C2
ARV1	NM_001346992.2		c.283A>C	p.Thr95Pro	missense	Exon 2 of 7	NP_001333921.1
ARV1	NR_144538.2		n.295A>C		non_coding_transcript_exon	Exon 2 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARV1	ENST00000310256.7	TSL:1 MANE Select	c.283A>C	p.Thr95Pro	missense	Exon 2 of 6	ENSP00000312458.2	Q9H2C2
ARV1	ENST00000893839.1		c.283A>C	p.Thr95Pro	missense	Exon 2 of 7	ENSP00000563898.1
ARV1	ENST00000893842.1		c.283A>C	p.Thr95Pro	missense	Exon 2 of 6	ENSP00000563901.1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000411

AC:

AN:

219174

AF XY:

0.0000336

show subpopulations

Gnomad AFR exome

AF:

0.000341

Gnomad AMR exome

AF:

0.000158

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1400768

Hom.:

Cov.:

AF XY:

0.0000115

AC XY:

AN XY:

695546

show subpopulations

African (AFR)

AF:

0.000384

AC:

AN:

31226

American (AMR)

AF:

0.000189

AC:

AN:

37036

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24848

East Asian (EAS)

AF:

0.00

AC:

AN:

37740

South Asian (SAS)

AF:

0.00

AC:

AN:

75032

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5606

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1079034

Other (OTH)

AF:

0.0000518

AC:

AN:

57950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.000118

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.000409

AC:

AN:

41564

American (AMR)

AF:

0.00

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

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:

0.0000331

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ARV1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Uncertain

0.071

BayesDel_noAF

Pathogenic

0.16

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.80

M_CAP

Benign

0.061

MetaRNN

Uncertain

0.56

MetaSVM

Benign

-0.80

MutationAssessor

Pathogenic

3.0

PhyloP100

8.9

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.46

Sift

Uncertain

0.011

Sift4G

Uncertain

0.056

Polyphen

0.99

Vest4

0.67

MVP

0.92

MPC

0.78

ClinPred

0.70

GERP RS

4.9

Varity_R

0.84

gMVP

0.85

Mutation Taster

=22/78

disease causing

(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

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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