NM_001126111.3:c.434A>T

Variant names:

• chr8-89914652-A-T
• NM_001126111.3:c.434A>T

Variant summary

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

The NM_001126111.3(OSGIN2):​c.434A>T​(p.Tyr145Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OSGIN2 NM_001126111.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.97

Genes affected

OSGIN2 (HGNC:1355): (oxidative stress induced growth inhibitor family member 2) Predicted to enable growth factor activity. Predicted to be involved in negative regulation of cell growth. [provided by Alliance of Genome Resources, Apr 2022]

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 (MetaRNN=0.1251922).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSGIN2	NM_001126111.3	c.434A>T	p.Tyr145Phe	missense_variant	Exon 4 of 6	ENST00000451899.7	NP_001119583.1
OSGIN2	NM_004337.2	c.302A>T	p.Tyr101Phe	missense_variant	Exon 4 of 6		NP_004328.1
OSGIN2	XM_011517287.4	c.302A>T	p.Tyr101Phe	missense_variant	Exon 4 of 6		XP_011515589.1
OSGIN2	XM_011517288.4	c.-615A>T		upstream_gene_variant			XP_011515590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSGIN2	ENST00000451899.7	c.434A>T	p.Tyr145Phe	missense_variant	Exon 4 of 6	1	NM_001126111.3	ENSP00000396445.2
OSGIN2	ENST00000297438.6	c.302A>T	p.Tyr101Phe	missense_variant	Exon 4 of 6	1		ENSP00000297438.2
OSGIN2	ENST00000647849.1	c.302A>T	p.Tyr101Phe	missense_variant	Exon 4 of 6			ENSP00000497119.1
OSGIN2	ENST00000520659.1	c.434A>T	p.Tyr145Phe	missense_variant	Exon 4 of 5	2		ENSP00000431029.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.434A>T (p.Y145F) alteration is located in exon 4 (coding exon 4) of the OSGIN2 gene. This alteration results from a A to T substitution at nucleotide position 434, causing the tyrosine (Y) at amino acid position 145 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Benign	0.92
DEOGEN2	Benign	0.024	T;T;.;.
Eigen	Benign	-0.16
Eigen_PC	Benign	0.061
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.86	.;D;D;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.63	N;N;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.92	.;N;N;N
REVEL	Benign	0.040
Sift	Benign	0.66	.;T;T;T
Sift4G	Benign	0.68	.;T;T;T
Polyphen		0.0070	B;B;B;.
Vest4		0.29, 0.28, 0.28
MutPred		0.28		Gain of helix (P = 0.0199);Gain of helix (P = 0.0199);.;.;
MVP		0.26
MPC		0.32
ClinPred		0.32	T
GERP RS		5.7
Varity_R		0.070
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-90926880;