12-6944745-C-T

Variant names:

• chr12-6944745-C-T
• rs744167
• NM_138425.4:c.229+93C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_138425.4(C12orf57):​c.229+93C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,574,308 control chromosomes in the GnomAD database, including 20,471 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1750 hom., cov: 33)
  • Exomes 𝑓: 0.15 (18721 hom.)
• Consequence: C12orf57 NM_138425.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0460
• Publications: 10 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]

C12orf57 Gene-Disease associations (from GenCC):

• temtamy syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000272173 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 12-6944745-C-T is Benign according to our data. Variant chr12-6944745-C-T is described in ClinVar as Benign. ClinVar VariationId is 1264683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138425.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C12orf57	NM_138425.4	MANE Select	c.229+93C>T		intron	N/A	NP_612434.1
	C12orf57	NM_001301834.1		c.229+93C>T		intron	N/A	NP_001288763.1
	C12orf57	NM_001301836.2		c.190+93C>T		intron	N/A	NP_001288765.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C12orf57	ENST00000229281.6	TSL:1 MANE Select	c.229+93C>T		intron	N/A	ENSP00000229281.5
	C12orf57	ENST00000544681.1	TSL:2	c.*10C>T		3_prime_UTR	Exon 2 of 2	ENSP00000475422.1
	C12orf57	ENST00000852280.1		c.229+93C>T		intron	N/A	ENSP00000522339.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19312 AN: 152050 Hom.: 1745 Cov.: 33

Gnomad AFR AF: 0.0305

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.107

GnomAD2 exomes AF: 0.190 AC: 40873 AN: 214620 AF XY: 0.180

Gnomad AFR exome AF: 0.0270

Gnomad AMR exome AF: 0.411

Gnomad ASJ exome AF: 0.111

Gnomad EAS exome AF: 0.219

Gnomad FIN exome AF: 0.173

Gnomad NFE exome AF: 0.147

Gnomad OTH exome AF: 0.170

GnomAD4 exome AF: 0.153 AC: 217040 AN: 1422140 Hom.: 18721 Cov.: 32 AF XY: 0.152 AC XY: 106581 AN XY: 700970

African (AFR) AF: 0.0227 AC: 743 AN: 32794

American (AMR) AF: 0.393 AC: 16742 AN: 42562

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2648 AN: 24332

East Asian (EAS) AF: 0.212 AC: 8224 AN: 38846

South Asian (SAS) AF: 0.172 AC: 14279 AN: 82804

European-Finnish (FIN) AF: 0.174 AC: 8789 AN: 50418

Middle Eastern (MID) AF: 0.0722 AC: 405 AN: 5612

European-Non Finnish (NFE) AF: 0.144 AC: 156915 AN: 1086308

Other (OTH) AF: 0.142 AC: 8295 AN: 58464

GnomAD4 genome AF: 0.127 AC: 19326 AN: 152168 Hom.: 1750 Cov.: 33 AF XY: 0.132 AC XY: 9812 AN XY: 74388

African (AFR) AF: 0.0304 AC: 1262 AN: 41534

American (AMR) AF: 0.251 AC: 3841 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 376 AN: 3466

East Asian (EAS) AF: 0.216 AC: 1118 AN: 5164

South Asian (SAS) AF: 0.183 AC: 880 AN: 4820

European-Finnish (FIN) AF: 0.170 AC: 1797 AN: 10600

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.143 AC: 9696 AN: 67978

Other (OTH) AF: 0.107 AC: 225 AN: 2110

Alfa AF: 0.137 Hom.: 3325

Bravo AF: 0.132

Asia WGS AF: 0.221 AC: 766 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: 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	-0.68
CADD	Benign	4.7
DANN	Benign	0.84
PhyloP100		0.046
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs744167; hg19: chr12-7053908; COSMIC: COSV57547369; COSMIC: COSV57547369;