chr12-6943816-C-T

Variant names:

• chr12-6943816-C-T
• rs115670517
• NM_001301834.1:c.-16+154C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_001301834.1(C12orf57):​c.-16+154C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 833,580 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (2 hom.)
• Consequence: C12orf57 NM_001301834.1 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.30
• Publications: 0 publications found

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]

RNU7-1 (HGNC:34033): (RNA, U7 small nuclear 1) Implicated in Aicardi-Goutieres syndrome. [provided by Alliance of Genome Resources, Apr 2022]

RNU7-1 Gene-Disease associations (from GenCC):

• Aicardi-Goutieres syndrome 9

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), PanelApp Australia

ENSG00000272173 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00267 (407/152352) while in subpopulation AFR AF = 0.00712 (296/41588). AF 95% confidence interval is 0.00645. There are 0 homozygotes in GnomAd4. There are 197 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301834.1. 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
	C12orf57	NM_001301834.1		c.-16+154C>T		intron	N/A	NP_001288763.1	Q99622
	C12orf57	NM_001301836.2		c.13+154C>T		intron	N/A	NP_001288765.1
	RNU7-1	NR_023317.1		n.1C>T		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C12orf57	ENST00000852280.1		c.-16+154C>T		intron	N/A	ENSP00000522339.1
	C12orf57	ENST00000545581.5	TSL:3	c.-16+154C>T		intron	N/A	ENSP00000440602.1	Q99622
	RNU7-1	ENST00000458811.1	TSL:6	n.1C>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.00265 AC: 404 AN: 152234 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00707

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000852

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00108 AC: 736 AN: 681228 Hom.: 2 Cov.: 9 AF XY: 0.00100 AC XY: 343 AN XY: 342664

African (AFR) AF: 0.00796 AC: 123 AN: 15456

American (AMR) AF: 0.00122 AC: 18 AN: 14696

Ashkenazi Jewish (ASJ) AF: 0.00703 AC: 82 AN: 11672

East Asian (EAS) AF: 0.000197 AC: 4 AN: 20282

South Asian (SAS) AF: 0.000374 AC: 19 AN: 50824

European-Finnish (FIN) AF: 0.0000656 AC: 1 AN: 15234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2192

European-Non Finnish (NFE) AF: 0.000850 AC: 443 AN: 521280

Other (OTH) AF: 0.00155 AC: 46 AN: 29592

GnomAD4 genome AF: 0.00267 AC: 407 AN: 152352 Hom.: 0 Cov.: 33 AF XY: 0.00264 AC XY: 197 AN XY: 74506

African (AFR) AF: 0.00712 AC: 296 AN: 41588

American (AMR) AF: 0.00176 AC: 27 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000853 AC: 58 AN: 68028

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00330

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.0010
DANN	Benign	0.65
PhyloP100		-2.3
PromoterAI		0.0063	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Other links and lift over

dbSNP: rs115670517; hg19: chr12-7052979;