rs149374821

Variant names:

• chr12-6943867-C-T
• rs149374821
• ENST00000544681.1:c.-255C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-6943867-C-T
• chr12-6943867-C-A
• chr12-6943867-C-G

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+205C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 939,128 control chromosomes in the GnomAD database, including 186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (20 hom., cov: 33)
  • Exomes 𝑓: 0.019 (166 hom.)
• Consequence: C12orf57 NM_001301834.1 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.752
• Publications: 1 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=-0.62).
• BP6: Variant 12-6943867-C-T is Benign according to our data. Variant chr12-6943867-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1301050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0154 (2344/152260) while in subpopulation AMR AF = 0.0223 (341/15294). AF 95% confidence interval is 0.0203. There are 20 homozygotes in GnomAd4. There are 1077 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 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+205C>T		intron	N/A	NP_001288763.1	Q99622
	C12orf57	NM_001301836.2		c.13+205C>T		intron	N/A	NP_001288765.1
	RNU7-1	NR_023317.1		n.52C>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.-255C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000475422.1	U3KQ07
	C12orf57	ENST00000537087.5	TSL:2	c.-255C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000440937.1	F5GXW5
	C12orf57	ENST00000921170.1		c.-255C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000591229.1

Frequencies

GnomAD3 genomes AF: 0.0154 AC: 2343 AN: 152142 Hom.: 20 Cov.: 33

Gnomad AFR AF: 0.00956

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0223

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00643

Gnomad FIN AF: 0.00755

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0191

Gnomad OTH AF: 0.0211

GnomAD4 exome AF: 0.0186 AC: 14674 AN: 786868 Hom.: 166 Cov.: 10 AF XY: 0.0187 AC XY: 7373 AN XY: 394480

African (AFR) AF: 0.00838 AC: 148 AN: 17654

American (AMR) AF: 0.0228 AC: 387 AN: 16958

Ashkenazi Jewish (ASJ) AF: 0.0299 AC: 435 AN: 14560

East Asian (EAS) AF: 0.000931 AC: 26 AN: 27920

South Asian (SAS) AF: 0.00909 AC: 476 AN: 52384

European-Finnish (FIN) AF: 0.00767 AC: 175 AN: 22802

Middle Eastern (MID) AF: 0.00968 AC: 25 AN: 2582

European-Non Finnish (NFE) AF: 0.0208 AC: 12400 AN: 596514

Other (OTH) AF: 0.0170 AC: 602 AN: 35494

GnomAD4 genome AF: 0.0154 AC: 2344 AN: 152260 Hom.: 20 Cov.: 33 AF XY: 0.0145 AC XY: 1077 AN XY: 74440

African (AFR) AF: 0.00953 AC: 396 AN: 41560

American (AMR) AF: 0.0223 AC: 341 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5182

South Asian (SAS) AF: 0.00644 AC: 31 AN: 4816

European-Finnish (FIN) AF: 0.00755 AC: 80 AN: 10594

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

European-Non Finnish (NFE) AF: 0.0191 AC: 1299 AN: 68024

Other (OTH) AF: 0.0213 AC: 45 AN: 2112

Alfa AF: 0.00429 Hom.: 0

Bravo AF: 0.0164

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	-0.62
CADD	Benign	0.058
DANN	Benign	0.72
PhyloP100		-0.75
PromoterAI		-0.18	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: rs149374821; hg19: chr12-7053030;