chr12-6943811-C-T

Variant names:

• chr12-6943811-C-T
• rs76168000
• NM_001301834.1:c.-16+149C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001301834.1(C12orf57):​c.-16+149C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0056 in 858,098 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (86 hom., cov: 33)
  • Exomes 𝑓: 0.0028 (45 hom.)
• Consequence: C12orf57 NM_001301834.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.23
• 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=-0.66).
• BP6: Variant 12-6943811-C-T is Benign according to our data. Variant chr12-6943811-C-T is described in ClinVar as Benign. ClinVar VariationId is 1266944.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0598 is higher than 0.05.

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+149C>T		intron	N/A	NP_001288763.1	Q99622
	C12orf57	NM_001301836.2		c.13+149C>T		intron	N/A	NP_001288765.1
	C12orf57	NM_138425.4	MANE Select	c.-311C>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+149C>T		intron	N/A	ENSP00000522339.1
	C12orf57	ENST00000545581.5	TSL:3	c.-16+149C>T		intron	N/A	ENSP00000440602.1	Q99622
	ENSG00000272173	ENST00000607421.3	TSL:6	n.913G>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0185 AC: 2815 AN: 152206 Hom.: 86 Cov.: 33

Gnomad AFR AF: 0.0620

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.00956

GnomAD4 exome AF: 0.00283 AC: 1994 AN: 705774 Hom.: 45 Cov.: 9 AF XY: 0.00298 AC XY: 1055 AN XY: 353744

African (AFR) AF: 0.0607 AC: 962 AN: 15858

American (AMR) AF: 0.00622 AC: 90 AN: 14478

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11606

East Asian (EAS) AF: 0.000103 AC: 2 AN: 19332

South Asian (SAS) AF: 0.0130 AC: 668 AN: 51424

European-Finnish (FIN) AF: 0.000139 AC: 2 AN: 14408

Middle Eastern (MID) AF: 0.00353 AC: 8 AN: 2264

European-Non Finnish (NFE) AF: 0.000262 AC: 143 AN: 546288

Other (OTH) AF: 0.00395 AC: 119 AN: 30116

GnomAD4 genome AF: 0.0185 AC: 2812 AN: 152324 Hom.: 86 Cov.: 33 AF XY: 0.0183 AC XY: 1363 AN XY: 74494

African (AFR) AF: 0.0618 AC: 2568 AN: 41560

American (AMR) AF: 0.00751 AC: 115 AN: 15304

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.0151 AC: 73 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000485 AC: 33 AN: 68042

Other (OTH) AF: 0.00946 AC: 20 AN: 2114

Alfa AF: 0.00344 Hom.: 2

Bravo AF: 0.0203

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.66
CADD	Benign	0.0020
DANN	Benign	0.62
PhyloP100		-3.2
PromoterAI		-0.20	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: rs76168000; hg19: chr12-7052974;