12-87986336-A-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/20 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

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

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=0.15651748).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C12orf50	NM_152589.3	c.898T>C	p.Phe300Leu	missense_variant	Exon 10 of 13	ENST00000298699.7	NP_689802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C12orf50	ENST00000298699.7	c.898T>C	p.Phe300Leu	missense_variant	Exon 10 of 13	2	NM_152589.3	ENSP00000298699.2
C12orf50	ENST00000551944.1	n.1192T>C		non_coding_transcript_exon_variant	Exon 9 of 10	1
C12orf50	ENST00000550553.5	c.781T>C	p.Phe261Leu	missense_variant	Exon 9 of 12	5		ENSP00000448344.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 23, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.898T>C (p.F300L) alteration is located in exon 10 (coding exon 9) of the C12orf50 gene. This alteration results from a T to C substitution at nucleotide position 898, causing the phenylalanine (F) at amino acid position 300 to be replaced by a leucine (L). 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	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;T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.2	M;.
PROVEAN	Benign	-0.34	N;N
REVEL	Benign	0.11
Sift	Benign	0.052	T;T
Sift4G	Benign	0.25	T;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-88380113;