12-6943813-C-T

Variant names:

• chr12-6943813-C-T
• rs142699589
• NM_001301834.1:c.-16+151C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001301834.1(C12orf57):​c.-16+151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 865,876 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00053 (5 hom.)
• Consequence: C12orf57 NM_001301834.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.21
• 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]

ENSG00000272173 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 12-6943813-C-T is Benign according to our data. Variant chr12-6943813-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1300813.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00394 (601/152374) while in subpopulation AFR AF = 0.0132 (549/41590). AF 95% confidence interval is 0.0123. There are 1 homozygotes in GnomAd4. There are 272 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 5 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+151C>T		intron	N/A	NP_001288763.1	Q99622
	C12orf57	NM_001301836.2		c.13+151C>T		intron	N/A	NP_001288765.1
	C12orf57	NM_138425.4	MANE Select	c.-309C>T		upstream_gene	N/A	NP_612434.1	Q99622

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C12orf57	ENST00000852280.1		c.-16+151C>T		intron	N/A	ENSP00000522339.1
	C12orf57	ENST00000545581.5	TSL:3	c.-16+151C>T		intron	N/A	ENSP00000440602.1	Q99622
	ENSG00000272173	ENST00000607421.3	TSL:6	n.911G>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.00395 AC: 601 AN: 152256 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.000530 AC: 378 AN: 713502 Hom.: 5 Cov.: 9 AF XY: 0.000501 AC XY: 179 AN XY: 357410

African (AFR) AF: 0.0123 AC: 196 AN: 15910

American (AMR) AF: 0.000545 AC: 8 AN: 14674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11818

East Asian (EAS) AF: 0.000352 AC: 7 AN: 19914

South Asian (SAS) AF: 0.000272 AC: 14 AN: 51406

European-Finnish (FIN) AF: 0.0000673 AC: 1 AN: 14868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2298

European-Non Finnish (NFE) AF: 0.000223 AC: 123 AN: 552110

Other (OTH) AF: 0.000951 AC: 29 AN: 30504

GnomAD4 genome AF: 0.00394 AC: 601 AN: 152374 Hom.: 1 Cov.: 33 AF XY: 0.00365 AC XY: 272 AN XY: 74524

African (AFR) AF: 0.0132 AC: 549 AN: 41590

American (AMR) AF: 0.00183 AC: 28 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

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

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10628

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

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68038

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000106 Hom.: 0

Bravo AF: 0.00482

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

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	-0.62
CADD	Benign	0.0020
DANN	Benign	0.60
PhyloP100		-3.2
PromoterAI		0.0064	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Other links and lift over

dbSNP: rs142699589; hg19: chr12-7052976;