12-14813670-C-T

Variant names:

• chr12-14813670-C-T
• rs4764124
• NM_175874.4:c.-24-9242C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175874.4(C12orf60):​c.-24-9242C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,886 control chromosomes in the GnomAD database, including 20,224 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (20224 hom., cov: 31)
• Consequence: C12orf60 NM_175874.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• Publications: 19 publications found

Genes affected

C12orf60 (HGNC:28726): (chromosome 12 open reading frame 60)

SMCO3 (HGNC:34401): (single-pass membrane protein with coiled-coil domains 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000256339 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175874.4. 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
	C12orf60	NM_175874.4	MANE Select	c.-24-9242C>T		intron	N/A	NP_787070.2	Q5U649
	SMCO3	NM_001013698.2	MANE Select	c.-17+456G>A		intron	N/A	NP_001013720.2	A2RU48

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C12orf60	ENST00000330828.3	TSL:1 MANE Select	c.-24-9242C>T		intron	N/A	ENSP00000331691.2	Q5U649
	SMCO3	ENST00000316048.2	TSL:1 MANE Select	c.-17+456G>A		intron	N/A	ENSP00000381895.1	A2RU48
	C12orf60	ENST00000857839.1		c.-24-9242C>T		intron	N/A	ENSP00000527898.1

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77335 AN: 151768 Hom.: 20167 Cov.: 31

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.498

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.510 AC: 77454 AN: 151886 Hom.: 20224 Cov.: 31 AF XY: 0.509 AC XY: 37744 AN XY: 74210

African (AFR) AF: 0.607 AC: 25129 AN: 41424

American (AMR) AF: 0.567 AC: 8657 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1714 AN: 3470

East Asian (EAS) AF: 0.231 AC: 1197 AN: 5174

South Asian (SAS) AF: 0.495 AC: 2378 AN: 4804

European-Finnish (FIN) AF: 0.451 AC: 4747 AN: 10526

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31886 AN: 67908

Other (OTH) AF: 0.501 AC: 1057 AN: 2108

Alfa AF: 0.493 Hom.: 13910

Bravo AF: 0.523

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.035
DANN	Benign	0.46
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs4764124; hg19: chr12-14966604;