NM_152589.3:c.898T>C

Variant names:

• chr12-87986336-A-G
• NM_152589.3:c.898T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152589.3(C12orf50):​c.898T>C​(p.Phe300Leu) variant causes a missense 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. 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: C12orf50 NM_152589.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.34
• Publications: 0 publications found

Genes affected

C12orf50 (HGNC:26665): (chromosome 12 open reading frame 50) Predicted to enable mRNA binding activity. Predicted to be involved in poly(A)+ mRNA export from nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15651748).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152589.3. 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
	C12orf50	NM_152589.3	MANE Select	c.898T>C	p.Phe300Leu	missense	Exon 10 of 13	NP_689802.1	Q8NA57
	C12orf50	NM_001363616.2		c.781T>C	p.Phe261Leu	missense	Exon 9 of 12	NP_001350545.1	F8VSD7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C12orf50	ENST00000298699.7	TSL:2 MANE Select	c.898T>C	p.Phe300Leu	missense	Exon 10 of 13	ENSP00000298699.2	Q8NA57
	C12orf50	ENST00000551944.1	TSL:1	n.1192T>C		non_coding_transcript_exon	Exon 9 of 10
	C12orf50	ENST00000550553.5	TSL:5	c.781T>C	p.Phe261Leu	missense	Exon 9 of 12	ENSP00000448344.1	F8VSD7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.89
DEOGEN2	Benign	0.0043	T
Eigen	Benign	0.077
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.3
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.11
Sift	Benign	0.052	T
Sift4G	Benign	0.25	T
Polyphen		0.57	P
Vest4		0.30
MutPred		0.16		Gain of glycosylation at P301 (P = 0.1202)
MVP		0.37
MPC		0.090
ClinPred		0.24	T
GERP RS		4.7
Varity_R		0.099
gMVP		0.12
Mutation Taster		=99/1	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

hg19: chr12-88380113;