Variant 19-17301557-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024527.5(ABHD8):c.60C>T(p.Ala20=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,602,192 control chromosomes in the GnomAD database, including 70,527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5431 hom., cov: 33)

Exomes 𝑓: 0.30 ( 65096 hom. )

Consequence

ABHD8
NM_024527.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.15

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]

ABHD8 links:

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]

MRPL34 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 19-17301557-G-A is Benign according to our data. Variant chr19-17301557-G-A is described in ClinVar as [Benign]. Clinvar id is 1296712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.15 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ABHD8	NM_024527.5 linkuse as main transcript	c.60C>T	p.Ala20=	synonymous_variant	2/5	ENST00000247706.4
MRPL34	NM_001400072.1 linkuse as main transcript	c.-62-4274G>A		intron_variant
MRPL34	NM_001400073.1 linkuse as main transcript	c.-63+3180G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABHD8	ENST00000247706.4 linkuse as main transcript	c.60C>T	p.Ala20=	synonymous_variant	2/5	1	NM_024527.5	P1

Frequencies

GnomAD3 genomes

AF:

0.259

AC:

39402

AN:

152054

Hom.:

5420

Cov.:

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.336

Gnomad AMR

AF:

0.271

Gnomad ASJ

AF:

0.295

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.374

Gnomad FIN

AF:

0.303

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.300

Gnomad OTH

AF:

0.251

GnomAD3 exomes

AF:

0.286

AC:

68377

AN:

239430

Hom.:

10179

AF XY:

0.292

AC XY:

38127

AN XY:

130768

show subpopulations

Gnomad AFR exome

AF:

0.166

Gnomad AMR exome

AF:

0.293

Gnomad ASJ exome

AF:

0.298

Gnomad EAS exome

AF:

0.111

Gnomad SAS exome

AF:

0.374

Gnomad FIN exome

AF:

0.304

Gnomad NFE exome

AF:

0.300

Gnomad OTH exome

AF:

0.290

GnomAD4 exome

AF:

0.297

AC:

430259

AN:

1450020

Hom.:

65096

Cov.:

AF XY:

0.299

AC XY:

215126

AN XY:

720084

show subpopulations

Gnomad4 AFR exome

AF:

0.167

Gnomad4 AMR exome

AF:

0.289

Gnomad4 ASJ exome

AF:

0.293

Gnomad4 EAS exome

AF:

0.0961

Gnomad4 SAS exome

AF:

0.368

Gnomad4 FIN exome

AF:

0.305

Gnomad4 NFE exome

AF:

0.302

Gnomad4 OTH exome

AF:

0.300

GnomAD4 genome

AF:

0.259

AC:

39437

AN:

152172

Hom.:

5431

Cov.:

AF XY:

0.259

AC XY:

19300

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.177

Gnomad4 AMR

AF:

0.271

Gnomad4 ASJ

AF:

0.295

Gnomad4 EAS

AF:

0.115

Gnomad4 SAS

AF:

0.376

Gnomad4 FIN

AF:

0.303

Gnomad4 NFE

AF:

0.300

Gnomad4 OTH

AF:

0.259

Alfa

AF:

0.282

Hom.:

3060

Bravo

AF:

0.250

Asia WGS

AF:

0.264

AC:

916

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 04, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

2.0

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over