chr19-17301216-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024527.5(ABHD8):​c.401G>A​(p.Gly134Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000689 in 1,597,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

ABHD8
NM_024527.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.150
Variant links:
Genes affected
ABHD8 (HGNC:23759): (abhydrolase domain containing 8) This gene is upstream of, and in a head-to-head orientation with the gene for the mitochondrial ribosomal protein L34. The predicted protein contains alpha/beta hydrolase fold and secretory lipase domains. [provided by RefSeq, Jul 2008]
MRPL34 (HGNC:14488): (mitochondrial ribosomal protein L34) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09801644).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ABHD8NM_024527.5 linkuse as main transcriptc.401G>A p.Gly134Asp missense_variant 2/5 ENST00000247706.4
MRPL34NM_001400072.1 linkuse as main transcriptc.-62-4615C>T intron_variant
MRPL34NM_001400073.1 linkuse as main transcriptc.-63+2839C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ABHD8ENST00000247706.4 linkuse as main transcriptc.401G>A p.Gly134Asp missense_variant 2/51 NM_024527.5 P1
ABHD8ENST00000593489.1 linkuse as main transcriptc.449G>A p.Gly150Asp missense_variant 2/24
MRPL34ENST00000595444.1 linkuse as main transcriptc.215-4615C>T intron_variant 3
MRPL34ENST00000600434.5 linkuse as main transcriptc.-63+2839C>T intron_variant 3 P1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152242
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000145
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:
0.00
GnomAD3 exomes
AF:
0.00000453
AC:
1
AN:
220822
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
123004
show subpopulations
Gnomad AFR exome
AF:
0.0000767
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS 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:
0.00000346
AC:
5
AN:
1444772
Hom.:
0
Cov.:
30
AF XY:
0.00000139
AC XY:
1
AN XY:
718422
show subpopulations
Gnomad4 AFR exome
AF:
0.000152
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152242
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.000145
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 15, 2021The c.401G>A (p.G134D) alteration is located in exon 2 (coding exon 1) of the ABHD8 gene. This alteration results from a G to A substitution at nucleotide position 401, causing the glycine (G) at amino acid position 134 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
3.4
DANN
Benign
0.79
DEOGEN2
Benign
0.0053
T;.
Eigen
Benign
-0.80
Eigen_PC
Benign
-0.82
FATHMM_MKL
Benign
0.22
N
LIST_S2
Benign
0.48
T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.098
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L;.
MutationTaster
Benign
0.98
N
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-0.020
N;.
REVEL
Benign
0.097
Sift
Benign
0.56
T;.
Sift4G
Benign
0.084
T;T
Polyphen
0.39
B;.
Vest4
0.15
MutPred
0.25
Gain of relative solvent accessibility (P = 0.0082);.;
MVP
0.44
MPC
0.97
ClinPred
0.073
T
GERP RS
2.9
Varity_R
0.089
gMVP
0.62

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs957002325; hg19: chr19-17412025; API