rs114309358

Variant names:

• chr12-6943745-G-A
• rs114309358
• NM_001301834.1:c.-16+83G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-6943745-G-A
• chr12-6943745-G-C
• chr12-6943745-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS1

The NM_001301834.1(C12orf57):​c.-16+83G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000335 in 1,201,194 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00051 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00031 (0 hom.)
• Consequence: C12orf57 NM_001301834.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.62

Genes affected

C12orf57 (HGNC:29521): (chromosome 12 open reading frame 57) This gene is ubiquitously expressed in human tissues. It is required for development of the human corpus callosum. Mutations in this gene are associated with Temtamy syndrome (TEMTYS). Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]

ENSG00000272173 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000514 (78/151632) while in subpopulation AMR AF= 0.00204 (31/15222). AF 95% confidence interval is 0.00147. There are 0 homozygotes in gnomad4. There are 42 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C12orf57	NM_001301834.1	c.-16+83G>A		intron_variant	Intron 1 of 3		NP_001288763.1
C12orf57	NM_001301836.2	c.13+83G>A		intron_variant	Intron 1 of 2		NP_001288765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C12orf57	ENST00000545581.5	c.-16+83G>A		intron_variant	Intron 1 of 3	3		ENSP00000440602.1
ENSG00000272173	ENST00000607421.2	n.886C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
C12orf57	ENST00000538392.1	n.388+83G>A		intron_variant	Intron 2 of 2	2
C12orf57	ENST00000542222.1	n.230+83G>A		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.000514 AC: 78 AN: 151632 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00204

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000561

Gnomad OTH AF: 0.00144

GnomAD4 exome AF: 0.000310 AC: 325 AN: 1049562 Hom.: 0 Cov.: 17 AF XY: 0.000281 AC XY: 144 AN XY: 512602

Gnomad4 AFR exome AF: 0.0000950

Gnomad4 AMR exome AF: 0.000792

Gnomad4 ASJ exome AF: 0.0000788

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000468

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000344

Gnomad4 OTH exome AF: 0.000205

GnomAD4 genome AF: 0.000514 AC: 78 AN: 151632 Hom.: 0 Cov.: 32 AF XY: 0.000567 AC XY: 42 AN XY: 74102

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.00204

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000561

Gnomad4 OTH AF: 0.00144

Bravo AF: 0.000491

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.0010
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs114309358; hg19: chr12-7052908;