Genetic Variant ARV1:p.Met1? (chr1-230979107-T-C) – ACMG Classification: Likely_pathogenic (8 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate

The NM_022786.3(ARV1):c.2T>C(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,607,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ARV1
NM_022786.3 start_lost

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 0.900

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 links:

TTC13 (HGNC:26204): (tetratricopeptide repeat domain 13)

TTC13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

PVS1

Start lost variant, next in-frame start position is after 6 pathogenic variants. Next in-frame start position is after 143 codons. Genomic position: 230990242. Lost 0.523 part of the original CDS.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 1-230979107-T-C is Pathogenic according to our data. Variant chr1-230979107-T-C is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 1339604.Status of the report is criteria_provided_single_submitter, 1 stars.

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.2T>C	p.Met1?	start_lost	Exon 1 of 6	NP_073623.1	Q9H2C2
ARV1	NM_001346992.2		c.2T>C	p.Met1?	start_lost	Exon 1 of 7	NP_001333921.1
ARV1	NR_144538.2		n.14T>C		non_coding_transcript_exon	Exon 1 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARV1	ENST00000310256.7	TSL:1 MANE Select	c.2T>C	p.Met1?	start_lost	Exon 1 of 6	ENSP00000312458.2	Q9H2C2
ARV1	ENST00000893839.1		c.2T>C	p.Met1?	start_lost	Exon 1 of 7	ENSP00000563898.1
ARV1	ENST00000893842.1		c.2T>C	p.Met1?	start_lost	Exon 1 of 6	ENSP00000563901.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000410

AC:

AN:

244150

AF XY:

0.00000756

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000900

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1455734

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724044

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33112

American (AMR)

AF:

0.00

AC:

AN:

43708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25876

East Asian (EAS)

AF:

0.00

AC:

AN:

39282

South Asian (SAS)

AF:

0.00

AC:

AN:

85678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52914

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5368

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1109706

Other (OTH)

AF:

0.00

AC:

AN:

60090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00000658

AC:

AN:

151968

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41390

American (AMR)

AF:

0.00

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67972

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Likely pathogenic

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Uncertain

0.050

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.55

LIST_S2

Uncertain

0.90

M_CAP

Uncertain

0.10

MetaRNN

Pathogenic

0.97

MetaSVM

Benign

-1.0

PhyloP100

0.90

PROVEAN

Benign

-0.39

REVEL

Benign

0.20

Sift

Uncertain

0.010

Sift4G

Uncertain

0.022

Polyphen

0.15

Vest4

0.80

MutPred

1.0

Gain of catalytic residue at M1 (P = 0.0192)

MVP

0.75

ClinPred

0.97

GERP RS

3.6

PromoterAI

-0.059

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.67

gMVP

0.74

Mutation Taster

=53/147

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over