10-26746610-AT-A

Position:

• chr10-26746610-AT-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001012750.3(ABI1):​c.*1959delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 869,248 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0040 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (1 hom.)
• Consequence: ABI1 NM_001012750.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.491

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]

PDSS1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 10-26746610-AT-A is Benign according to our data. Variant chr10-26746610-AT-A is described in ClinVar as [Likely_benign]. Clinvar id is 1196649.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 605 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABI1	NM_001012750.3	c.*1959delA		3_prime_UTR_variant	11/11	ENST00000376140.4	NP_001012768.1
PDSS1	NM_014317.5	c.*146delT		3_prime_UTR_variant	12/12	ENST00000376215.10	NP_055132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABI1	ENST00000376140.4	c.*1959delA		3_prime_UTR_variant	11/11	5	NM_001012750.3	ENSP00000365310.3
PDSS1	ENST00000376215.10	c.*146delT		3_prime_UTR_variant	12/12	1	NM_014317.5	ENSP00000365388.5

Frequencies

GnomAD3 genomes AF: 0.00399 AC: 604 AN: 151312 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00145

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000236

Gnomad OTH AF: 0.00336

GnomAD4 exome AF: 0.00187 AC: 1342 AN: 717828 Hom.: 1 Cov.: 9 AF XY: 0.00173 AC XY: 644 AN XY: 371720

Gnomad4 AFR exome AF: 0.0143

Gnomad4 AMR exome AF: 0.00161

Gnomad4 ASJ exome AF: 0.000936

Gnomad4 EAS exome AF: 0.000589

Gnomad4 SAS exome AF: 0.000604

Gnomad4 FIN exome AF: 0.00105

Gnomad4 NFE exome AF: 0.00176

Gnomad4 OTH exome AF: 0.00212

GnomAD4 genome AF: 0.00400 AC: 605 AN: 151420 Hom.: 2 Cov.: 32 AF XY: 0.00374 AC XY: 277 AN XY: 73968

Gnomad4 AFR AF: 0.0134

Gnomad4 AMR AF: 0.00145

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000236

Gnomad4 OTH AF: 0.00333

Bravo AF: 0.00465

Asia WGS AF: 0.000867 AC: 3 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 18, 2020

- -

Computational scores

Source: dbNSFP v4.3

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: rs67302665; hg19: chr10-27035539;