chr12-6943875-C-T

Variant names:

• chr12-6943875-C-T
• rs115355876
• ENST00000544681.1:c.-247C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001301834.1(C12orf57):​c.-16+213C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00578 in 974,422 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0088 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0052 (24 hom.)
• Consequence: C12orf57 NM_001301834.1 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.51
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 12-6943875-C-T is Benign according to our data. Variant chr12-6943875-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1301145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00876 (1334/152252) while in subpopulation AFR AF = 0.018 (747/41552). AF 95% confidence interval is 0.0169. There are 7 homozygotes in GnomAd4. There are 620 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 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+213C>T		intron	N/A	NP_001288763.1	Q99622
	C12orf57	NM_001301836.2		c.13+213C>T		intron	N/A	NP_001288765.1
	RNU7-1	NR_023317.1		n.60C>T		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C12orf57	ENST00000544681.1	TSL:2	c.-247C>T		5_prime_UTR	Exon 1 of 2	ENSP00000475422.1	U3KQ07
	C12orf57	ENST00000537087.5	TSL:2	c.-247C>T		5_prime_UTR	Exon 1 of 3	ENSP00000440937.1	F5GXW5
	C12orf57	ENST00000921170.1		c.-247C>T		5_prime_UTR	Exon 1 of 2	ENSP00000591229.1

Frequencies

GnomAD3 genomes AF: 0.00876 AC: 1333 AN: 152130 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.00721

Gnomad EAS AF: 0.00654

Gnomad SAS AF: 0.00746

Gnomad FIN AF: 0.000943

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00550

Gnomad OTH AF: 0.00814

GnomAD4 exome AF: 0.00523 AC: 4302 AN: 822170 Hom.: 24 Cov.: 11 AF XY: 0.00531 AC XY: 2186 AN XY: 411622

African (AFR) AF: 0.0166 AC: 305 AN: 18404

American (AMR) AF: 0.00461 AC: 81 AN: 17574

Ashkenazi Jewish (ASJ) AF: 0.00633 AC: 96 AN: 15174

East Asian (EAS) AF: 0.00645 AC: 189 AN: 29322

South Asian (SAS) AF: 0.00732 AC: 391 AN: 53406

European-Finnish (FIN) AF: 0.00119 AC: 29 AN: 24408

Middle Eastern (MID) AF: 0.00226 AC: 6 AN: 2658

European-Non Finnish (NFE) AF: 0.00479 AC: 2991 AN: 624180

Other (OTH) AF: 0.00578 AC: 214 AN: 37044

GnomAD4 genome AF: 0.00876 AC: 1334 AN: 152252 Hom.: 7 Cov.: 33 AF XY: 0.00833 AC XY: 620 AN XY: 74444

African (AFR) AF: 0.0180 AC: 747 AN: 41552

American (AMR) AF: 0.00588 AC: 90 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00721 AC: 25 AN: 3466

East Asian (EAS) AF: 0.00656 AC: 34 AN: 5186

South Asian (SAS) AF: 0.00746 AC: 36 AN: 4824

European-Finnish (FIN) AF: 0.000943 AC: 10 AN: 10602

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00550 AC: 374 AN: 68004

Other (OTH) AF: 0.00806 AC: 17 AN: 2110

Alfa AF: 0.00701 Hom.: 4

Bravo AF: 0.00976

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	12
DANN	Benign	0.72
PhyloP100		2.5
PromoterAI		0.023	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3
Mutation Taster		=300/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs115355876; hg19: chr12-7053038;