rs145994149

Variant names:

• chr12-6943864-T-C
• rs145994149
• ENST00000544681.1:c.-258T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-6943864-T-C
• chr12-6943864-T-A
• chr12-6943864-T-G

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+202T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 937,242 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (3 hom.)
• Consequence: C12orf57 NM_001301834.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.89
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 12-6943864-T-C is Benign according to our data. Variant chr12-6943864-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3024660.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00352 (536/152342) while in subpopulation AFR AF = 0.00693 (288/41576). AF 95% confidence interval is 0.00627. There are 2 homozygotes in GnomAd4. There are 250 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 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+202T>C		intron	N/A	NP_001288763.1	Q99622
	C12orf57	NM_001301836.2		c.13+202T>C		intron	N/A	NP_001288765.1
	RNU7-1	NR_023317.1		n.49T>C		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.-258T>C		5_prime_UTR	Exon 1 of 2	ENSP00000475422.1	U3KQ07
	C12orf57	ENST00000537087.5	TSL:2	c.-258T>C		5_prime_UTR	Exon 1 of 3	ENSP00000440937.1	F5GXW5
	C12orf57	ENST00000921170.1		c.-258T>C		5_prime_UTR	Exon 1 of 2	ENSP00000591229.1

Frequencies

GnomAD3 genomes AF: 0.00352 AC: 536 AN: 152224 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00695

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00103

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00247

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.00162 AC: 1272 AN: 784900 Hom.: 3 Cov.: 10 AF XY: 0.00153 AC XY: 602 AN XY: 393746

African (AFR) AF: 0.00543 AC: 96 AN: 17680

American (AMR) AF: 0.00154 AC: 26 AN: 16928

Ashkenazi Jewish (ASJ) AF: 0.00284 AC: 41 AN: 14424

East Asian (EAS) AF: 0.00 AC: 0 AN: 27726

South Asian (SAS) AF: 0.0000574 AC: 3 AN: 52306

European-Finnish (FIN) AF: 0.000177 AC: 4 AN: 22536

Middle Eastern (MID) AF: 0.00156 AC: 4 AN: 2566

European-Non Finnish (NFE) AF: 0.00174 AC: 1035 AN: 595346

Other (OTH) AF: 0.00178 AC: 63 AN: 35388

GnomAD4 genome AF: 0.00352 AC: 536 AN: 152342 Hom.: 2 Cov.: 33 AF XY: 0.00336 AC XY: 250 AN XY: 74492

African (AFR) AF: 0.00693 AC: 288 AN: 41576

American (AMR) AF: 0.00288 AC: 44 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00103 AC: 11 AN: 10628

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

European-Non Finnish (NFE) AF: 0.00247 AC: 168 AN: 68030

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00190 Hom.: 1

Bravo AF: 0.00356

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	-0.63
CADD	Benign	0.0010
DANN	Benign	0.70
PhyloP100		-2.9
PromoterAI		-0.013	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: rs145994149; hg19: chr12-7053027;