NM_139076.3:c.*249delG

Variant names:

• chr4-83462219-TC-T
• rs34610900
• NM_139076.3:c.*249delG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_139076.3(ABRAXAS1):​c.*249delG 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
• Publications: 5 publications found

Genes affected

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]

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139076.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABRAXAS1	NM_139076.3	MANE Select	c.*249delG		3_prime_UTR	Exon 9 of 9	NP_620775.2	Q6UWZ7-1
	MRPS18C	NM_016067.4	MANE Select	c.*1023delC		3_prime_UTR	Exon 6 of 6	NP_057151.1	Q9Y3D5
	ABRAXAS1	NM_001345962.2		c.*249delG		3_prime_UTR	Exon 8 of 8	NP_001332891.1	Q6UWZ7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABRAXAS1	ENST00000321945.12	TSL:1 MANE Select	c.*249delG		3_prime_UTR	Exon 9 of 9	ENSP00000369857.3	Q6UWZ7-1
	MRPS18C	ENST00000295491.9	TSL:1 MANE Select	c.*1023delC		3_prime_UTR	Exon 6 of 6	ENSP00000295491.4	Q9Y3D5
	ABRAXAS1	ENST00000856950.1		c.*249delG		3_prime_UTR	Exon 9 of 9	ENSP00000527009.1

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

African (AFR) AF: 0.152 AC: 1260 AN: 8290

American (AMR) AF: 0.511 AC: 4457 AN: 8718

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 2762 AN: 9820

East Asian (EAS) AF: 0.628 AC: 12074 AN: 19220

South Asian (SAS) AF: 0.441 AC: 11586 AN: 26286

European-Finnish (FIN) AF: 0.461 AC: 5878 AN: 12760

Middle Eastern (MID) AF: 0.252 AC: 325 AN: 1290

European-Non Finnish (NFE) AF: 0.395 AC: 66922 AN: 169574

Other (OTH) AF: 0.387 AC: 6611 AN: 17092

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

African (AFR) AF: 0.166 AC: 6896 AN: 41472

American (AMR) AF: 0.472 AC: 7205 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 999 AN: 3462

East Asian (EAS) AF: 0.664 AC: 3418 AN: 5148

South Asian (SAS) AF: 0.490 AC: 2363 AN: 4818

European-Finnish (FIN) AF: 0.453 AC: 4779 AN: 10542

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27728 AN: 67954

Other (OTH) AF: 0.342 AC: 721 AN: 2108

Alfa AF: 0.189 Hom.: 692

Bravo AF: 0.350

Asia WGS AF: 0.581 AC: 2016 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34610900; hg19: chr4-84383372;