12-131929734-G-A

Variant names:

• chr12-131929734-G-A
• rs754814461
• NM_025215.6:c.12G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_025215.6(PUS1):​c.12G>A​(p.Gln4Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PUS1 NM_025215.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.314
• Publications: 0 publications found

Genes affected

PUS1 (HGNC:15508): (pseudouridine synthase 1) This gene encodes a pseudouridine synthase that converts uridine to pseudouridine once it has been incorporated into an RNA molecule. The encoded enzyme may play an essential role in tRNA function and in stabilizing the secondary and tertiary structure of many RNAs. A mutation in this gene has been linked to mitochondrial myopathy and sideroblastic anemia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Sep 2009]

PUS1-AS1 (HGNC:40706): (PUS1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 12-131929734-G-A is Benign according to our data. Variant chr12-131929734-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2819926.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.314 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025215.6. 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
	PUS1	NM_025215.6	MANE Select	c.12G>A	p.Gln4Gln	synonymous	Exon 1 of 6	NP_079491.2	E5KMT5
	PUS1	NM_001002019.3		c.-10-173G>A		intron	N/A	NP_001002019.1	E5KMT6
	PUS1	NM_001002020.3		c.-10-173G>A		intron	N/A	NP_001002020.1	E5KMT6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PUS1	ENST00000376649.8	TSL:1 MANE Select	c.12G>A	p.Gln4Gln	synonymous	Exon 1 of 6	ENSP00000365837.3	Q9Y606-1
	PUS1	ENST00000443358.6	TSL:1	c.-10-173G>A		intron	N/A	ENSP00000392451.2	Q9Y606-2
	PUS1	ENST00000890860.1		c.12G>A	p.Gln4Gln	synonymous	Exon 1 of 6	ENSP00000560919.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1439516 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 716316

African (AFR) AF: 0.00 AC: 0 AN: 32600

American (AMR) AF: 0.00 AC: 0 AN: 43972

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25802

East Asian (EAS) AF: 0.00 AC: 0 AN: 38660

South Asian (SAS) AF: 0.00 AC: 0 AN: 84770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5218

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108146

Other (OTH) AF: 0.00 AC: 0 AN: 59862

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Likely 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
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.0
DANN	Benign	0.90
PhyloP100		-0.31
PromoterAI		-0.068	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2

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: rs754814461; hg19: chr12-132414279;