12-56042173-A-G

Variant names:

• chr12-56042173-A-G
• rs201248213
• NM_001029.5:c.3+4A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001029.5(RPS26):​c.3+4A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: RPS26 NM_001029.5 splice_region, intron
• Scores: Splicing: ADA: 0.9132
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53

Genes affected

RPS26 (HGNC:10414): (ribosomal protein S26) This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S26E family of ribosomal proteins. Mutations in this gene are found in Diamond-Blackfan anemia 10. There are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS26	NM_001029.5	c.3+4A>G		splice_region_variant, intron_variant	Intron 1 of 3	ENST00000646449.2	NP_001020.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS26	ENST00000646449.2	c.3+4A>G		splice_region_variant, intron_variant	Intron 1 of 3		NM_001029.5	ENSP00000496643.1
RPS26	ENST00000356464.10	c.3+4A>G		splice_region_variant, intron_variant	Intron 2 of 4	1		ENSP00000348849.5
RPS26	ENST00000552361.1	c.3+4A>G		splice_region_variant, intron_variant	Intron 2 of 4	5		ENSP00000450339.1
RPS26	ENST00000548590.1	n.30+4A>G		splice_region_variant, intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461840 Hom.: 0 Cov.: 35 AF XY: 0.00000413 AC XY: 3 AN XY: 727222

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.91
dbscSNV1_RF	Benign	0.59
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.29		Position offset: -22

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201248213; hg19: chr12-56435957;