Genetic Variant ABHD18:p.Ile60Thr (chr4-127989722-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001366038.3(ABHD18):c.-623T>C variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000141 in 1,421,088 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ABHD18
NM_001366038.3 5_prime_UTR_premature_start_codon_gain

Scores

Splicing: ADA: 0.0001368

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.51

Publications

0 publications found

Variant links:

Genes affected

ABHD18 (HGNC:26111): (abhydrolase domain containing 18) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ABHD18 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0937286).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366038.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABHD18	NM_001358451.3	MANE Select	c.179T>C	p.Ile60Thr	missense splice_region	Exon 4 of 13	NP_001345380.1	A0A2R8YEZ0
ABHD18	NM_001366038.3		c.-623T>C		5_prime_UTR_premature_start_codon_gain	Exon 4 of 14	NP_001352967.1
ABHD18	NM_001366045.1		c.-252T>C		5_prime_UTR_premature_start_codon_gain	Exon 4 of 13	NP_001352974.1	Q0P651-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABHD18	ENST00000645843.2	MANE Select	c.179T>C	p.Ile60Thr	missense splice_region	Exon 4 of 13	ENSP00000496010.1	A0A2R8YEZ0
ABHD18	ENST00000444616.5	TSL:5	c.179T>C	p.Ile60Thr	missense splice_region	Exon 4 of 11	ENSP00000397229.1	Q0P651-1
ABHD18	ENST00000388795.10	TSL:5	n.177+5299T>C		intron	N/A	ENSP00000373447.6	B7WP89

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1421088

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

703972

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32528

American (AMR)

AF:

0.00

AC:

AN:

38042

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25042

East Asian (EAS)

AF:

0.00

AC:

AN:

38962

South Asian (SAS)

AF:

0.00

AC:

AN:

79044

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51874

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5656

European-Non Finnish (NFE)

AF:

0.00000183

AC:

AN:

1091232

Other (OTH)

AF:

0.00

AC:

AN:

58708

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0296732), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

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

Cov.:

ClinVar

ClinVar submissions

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

0.065

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.0016

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0017

MetaRNN

Benign

0.094

MetaSVM

Benign

-1.1

PhyloP100

4.5

PROVEAN

Benign

0.87

REVEL

Benign

0.11

Sift

Benign

0.55

Sift4G

Benign

0.57

Polyphen

0.0

Vest4

0.20

MutPred

0.47

Gain of relative solvent accessibility (P = 0.0082)

MVP

0.38

MPC

0.16

ClinPred

0.48

GERP RS

4.7

Varity_R

0.089

gMVP

0.37

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00014

dbscSNV1_RF

Benign

0.018

SpliceAI score (max)

0.010

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