2-19353627-G-A

Variant names:

• chr2-19353627-G-A
• rs780326478
• NM_145260.3:c.179C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_145260.3(OSR1):​c.179C>T​(p.Pro60Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,272 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P60Q) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: OSR1 NM_145260.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.84
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSR1	NM_145260.3	c.179C>T	p.Pro60Leu	missense_variant	Exon 2 of 3	ENST00000272223.3	NP_660303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSR1	ENST00000272223.3	c.179C>T	p.Pro60Leu	missense_variant	Exon 2 of 3	1	NM_145260.3	ENSP00000272223.2
OSR1	ENST00000487581.1	n.3286C>T		non_coding_transcript_exon_variant	Exon 1 of 2	1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152272 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152272 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74396

African (AFR) AF: 0.0000241 AC: 1 AN: 41474

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68050

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		7.8
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.24
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.65
MutPred		0.46		Loss of relative solvent accessibility (P = 0.0676);
MVP		0.31
ClinPred		0.95	D
GERP RS		4.3
Varity_R		0.27
gMVP		0.59
Mutation Taster		=82/18	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

Other links and lift over

dbSNP: rs780326478; hg19: chr2-19553388;