4-83462219-TC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_139076.3(ABRAXAS1):c.*249del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (11364 hom., cov: 0)
  • Exomes 𝑓: 0.41 (24477 hom.)
• Consequence: ABRAXAS1 NM_139076.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.344

Genes affected

MRPS18C (HGNC:16633): (mitochondrial ribosomal protein S18C) 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 28S subunit protein that belongs to the ribosomal protein S18P family. The encoded protein is one of three that has significant sequence similarity to bacterial S18 proteins. The primary sequences of the three human mitochondrial S18 proteins are no more closely related to each other than they are to the prokaryotic S18 proteins. Pseudogenes corresponding to this gene are found on chromosomes 8p, 12p, 15q, and 22q. [provided by RefSeq, Jul 2008]

ABRAXAS1 (HGNC:25829): (abraxas 1, BRCA1 A complex subunit) This gene encodes a protein that binds to the C-terminal repeats of breast cancer 1 (BRCA1) through a phospho-SXXF motif. The encoded protein recruits ubiquitin interaction motif containing 1 protein to BRCA1 protein and is required for DNA damage resistance, DNA repair, and cell cycle checkpoint control. Pseudogenes of this gene are found on chromosomes 3 and 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 4-83462219-TC-T is Benign according to our data. Variant chr4-83462219-TC-T is described in ClinVar as [Benign]. Clinvar id is 1272768.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPS18C	NM_016067.4	c.*1023del		3_prime_UTR_variant	6/6	ENST00000295491.9
ABRAXAS1	NM_139076.3	c.*249del		3_prime_UTR_variant	9/9	ENST00000321945.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPS18C	ENST00000295491.9	c.*1023del		3_prime_UTR_variant	6/6	1	NM_016067.4	P1
ABRAXAS1	ENST00000321945.12	c.*249del		3_prime_UTR_variant	9/9	1	NM_139076.3	P1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54484 AN: 151862 Hom.: 11345 Cov.: 0

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.337

GnomAD4 exome AF: 0.410 AC: 111875 AN: 273050 Hom.: 24477 Cov.: 0 AF XY: 0.412 AC XY: 58217 AN XY: 141224

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.511

Gnomad4 ASJ exome AF: 0.281

Gnomad4 EAS exome AF: 0.628

Gnomad4 SAS exome AF: 0.441

Gnomad4 FIN exome AF: 0.461

Gnomad4 NFE exome AF: 0.395

Gnomad4 OTH exome AF: 0.387

GnomAD4 genome AF: 0.359 AC: 54531 AN: 151980 Hom.: 11364 Cov.: 0 AF XY: 0.368 AC XY: 27302 AN XY: 74282

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.342

Alfa AF: 0.189 Hom.: 692

Bravo AF: 0.350

Asia WGS AF: 0.581 AC: 2016 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

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: rs34610900; hg19: chr4-84383372;