2-19353461-C-G

Variant names:

• chr2-19353461-C-G
• NM_145260.3:c.345G>C
• OSR1 p.Pro115Pro

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_145260.3(OSR1):​c.345G>C​(p.Pro115Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P115P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: OSR1 NM_145260.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -8.09
• Publications: 0 publications found

Genes affected

OSR1 (HGNC:8111): (odd-skipped related transcription factor 1) Enables sequence-specific double-stranded DNA binding activity. Involved in negative regulation of ion transmembrane transporter activity; positive regulation of gastrulation; and pronephros development. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

OSR1 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=-8.09 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145260.3. 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
	OSR1	NM_145260.3	MANE Select	c.345G>C	p.Pro115Pro	synonymous	Exon 2 of 3	NP_660303.1	Q8TAX0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSR1	ENST00000272223.3	TSL:1 MANE Select	c.345G>C	p.Pro115Pro	synonymous	Exon 2 of 3	ENSP00000272223.2	Q8TAX0
	OSR1	ENST00000487581.1	TSL:1	n.3452G>C		non_coding_transcript_exon	Exon 1 of 2
	OSR1	ENST00000852234.1		c.345G>C	p.Pro115Pro	synonymous	Exon 2 of 3	ENSP00000522293.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.8
DANN	Benign	0.83
PhyloP100		-8.1
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-19553222;