chr12-6944654-TGGGTCAGACGCGGGAAGGC-T

Variant names:

• chr12-6944654-TGGGTCAGACGCGGGAAGGC-T
• rs199730337
• NM_138425.4:c.229+25_229+43delTCAGACGCGGGAAGGCGGG

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3 BP6_Very_Strong BA1

The NM_138425.4(C12orf57):​c.229+25_229+43delTCAGACGCGGGAAGGCGGG variant causes a intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,610,452 control chromosomes in the GnomAD database, including 1,090 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (386 hom., cov: 32)
  • Exomes 𝑓: 0.011 (704 hom.)
• Consequence: C12orf57 NM_138425.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 8.05
• Publications: 3 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 -15 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• BP6: Variant 12-6944654-TGGGTCAGACGCGGGAAGGC-T is Benign according to our data. Variant chr12-6944654-TGGGTCAGACGCGGGAAGGC-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 466308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 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+25_229+43delTCAGACGCGGGAAGGCGGG		intron	N/A	NP_612434.1
	C12orf57	NM_001301834.1		c.229+25_229+43delTCAGACGCGGGAAGGCGGG		intron	N/A	NP_001288763.1
	C12orf57	NM_001301836.2		c.190+25_190+43delTCAGACGCGGGAAGGCGGG		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+25_229+43delTCAGACGCGGGAAGGCGGG		intron	N/A	ENSP00000229281.5
	C12orf57	ENST00000544681.1	TSL:2	c.254_272delTCAGACGCGGGAAGGCGGG	p.Val85GlufsTer88	frameshift	Exon 2 of 2	ENSP00000475422.1
	C12orf57	ENST00000538392.1	TSL:2	n.590_608delTCAGACGCGGGAAGGCGGG		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0451 AC: 6856 AN: 151972 Hom.: 383 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0884

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.0336

Gnomad SAS AF: 0.00706

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00277

Gnomad OTH AF: 0.0411

GnomAD2 exomes AF: 0.0305 AC: 7625 AN: 250344 AF XY: 0.0235

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.124

Gnomad ASJ exome AF: 0.0214

Gnomad EAS exome AF: 0.0315

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00300

Gnomad OTH exome AF: 0.0212

GnomAD4 exome AF: 0.0112 AC: 16262 AN: 1458362 Hom.: 704 AF XY: 0.0101 AC XY: 7288 AN XY: 724718

African (AFR) AF: 0.123 AC: 4110 AN: 33366

American (AMR) AF: 0.118 AC: 5261 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 565 AN: 26106

East Asian (EAS) AF: 0.0346 AC: 1371 AN: 39586

South Asian (SAS) AF: 0.00750 AC: 647 AN: 86224

European-Finnish (FIN) AF: 0.000188 AC: 10 AN: 53118

Middle Eastern (MID) AF: 0.00990 AC: 57 AN: 5758

European-Non Finnish (NFE) AF: 0.00295 AC: 3276 AN: 1109340

Other (OTH) AF: 0.0160 AC: 965 AN: 60226

GnomAD4 genome AF: 0.0453 AC: 6888 AN: 152090 Hom.: 386 Cov.: 32 AF XY: 0.0449 AC XY: 3338 AN XY: 74346

African (AFR) AF: 0.120 AC: 4974 AN: 41472

American (AMR) AF: 0.0887 AC: 1355 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 69 AN: 3468

East Asian (EAS) AF: 0.0337 AC: 174 AN: 5162

South Asian (SAS) AF: 0.00686 AC: 33 AN: 4814

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10600

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00277 AC: 188 AN: 67980

Other (OTH) AF: 0.0421 AC: 89 AN: 2114

Alfa AF: 0.0112 Hom.: 9

Bravo AF: 0.0565

Asia WGS AF: 0.0230 AC: 81 AN: 3478

EpiCase AF: 0.00344

EpiControl AF: 0.00261

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Apr 14, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Apr 07, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Temtamy syndrome Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.1
Mutation Taster		=58/142	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs199730337; hg19: chr12-7053817; COSMIC: COSV57546964; COSMIC: COSV57546964;