10-26746630-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001012750.3(ABI1):c.*1940A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00792 in 756,810 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (90 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (57 hom.)
• Consequence: ABI1 NM_001012750.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.213

Genes affected

ABI1 (HGNC:11320): (abl interactor 1) This gene encodes a member of the Abelson-interactor family of adaptor proteins. These proteins facilitate signal transduction as components of several multiprotein complexes, and regulate actin polymerization and cytoskeletal remodeling through interactions with Abelson tyrosine kinases. The encoded protein plays a role in macropinocytosis as a component of the WAVE2 complex, and also forms a complex with EPS8 and SOS1 that mediates signal transduction from Ras to Rac. This gene may play a role in the progression of several malignancies including melanoma, colon cancer and breast cancer, and a t(10;11) chromosomal translocation involving this gene and the MLL gene has been associated with acute myeloid leukemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 14. [provided by RefSeq, Sep 2011]

PDSS1 (HGNC:17759): (decaprenyl diphosphate synthase subunit 1) The protein encoded by this gene is an enzyme that elongates the prenyl side-chain of coenzyme Q, or ubiquinone, one of the key elements in the respiratory chain. The gene product catalyzes the formation of all trans-polyprenyl pyrophosphates from isopentyl diphosphate in the assembly of polyisoprenoid side chains, the first step in coenzyme Q biosynthesis. The protein may be peripherally associated with the inner mitochondrial membrane, though no transit peptide has been definitively identified to date. Defects in this gene are a cause of coenzyme Q10 deficiency. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 10-26746630-T-G is Benign according to our data. Variant chr10-26746630-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 299706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABI1	NM_001012750.3	c.*1940A>C		3_prime_UTR_variant	11/11	ENST00000376140.4
PDSS1	NM_014317.5	c.*157T>G		3_prime_UTR_variant	12/12	ENST00000376215.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABI1	ENST00000376140.4	c.*1940A>C		3_prime_UTR_variant	11/11	5	NM_001012750.3
PDSS1	ENST00000376215.10	c.*157T>G		3_prime_UTR_variant	12/12	1	NM_014317.5	P1

Frequencies

GnomAD3 genomes AF: 0.0215 AC: 3277 AN: 152110 Hom.: 90 Cov.: 32

Gnomad AFR AF: 0.0691

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0123

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00673

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000955

Gnomad OTH AF: 0.0220

GnomAD4 exome AF: 0.00447 AC: 2702 AN: 604582 Hom.: 57 Cov.: 8 AF XY: 0.00453 AC XY: 1445 AN XY: 318824

Gnomad4 AFR exome AF: 0.0693

Gnomad4 AMR exome AF: 0.00747

Gnomad4 ASJ exome AF: 0.000797

Gnomad4 EAS exome AF: 0.00433

Gnomad4 SAS exome AF: 0.0113

Gnomad4 FIN exome AF: 0.00163

Gnomad4 NFE exome AF: 0.000785

Gnomad4 OTH exome AF: 0.00967

GnomAD4 genome AF: 0.0216 AC: 3291 AN: 152228 Hom.: 90 Cov.: 32 AF XY: 0.0204 AC XY: 1518 AN XY: 74430

Gnomad4 AFR AF: 0.0693

Gnomad4 AMR AF: 0.0124

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00675

Gnomad4 SAS AF: 0.0126

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.000956

Gnomad4 OTH AF: 0.0218

Alfa AF: 0.0154 Hom.: 12

Bravo AF: 0.0248

Asia WGS AF: 0.0210 AC: 71 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Deafness-encephaloneuropathy-obesity-valvulopathy syndrome Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Oct 08, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	13
Dann	Benign	0.76

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

Other links and lift over

dbSNP: rs1046187; hg19: chr10-27035559;