chr12-22062440-T-TATC

Variant names:

• chr12-22062440-T-TATC
• rs140406732
• NM_018686.6:c.1114+7_1114+9dupATC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000229329.7(CMAS):​c.1114+6_1114+7insATC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00506 in 1,611,100 control chromosomes in the GnomAD database, including 382 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (193 hom., cov: 31)
  • Exomes 𝑓: 0.0028 (189 hom.)
• Consequence: CMAS ENST00000229329.7 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.419
• Publications: 1 publications found

Genes affected

CMAS (HGNC:18290): (cytidine monophosphate N-acetylneuraminic acid synthetase) This gene encodes an enzyme that converts N-acetylneuraminic acid (NeuNAc) to cytidine 5'-monophosphate N-acetylneuraminic acid (CMP-NeuNAc). This process is important in the formation of sialylated glycoprotein and glycolipids. This modification plays a role in cell-cell communications and immune responses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

CMAS Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 12-22062440-T-TATC is Benign according to our data. Variant chr12-22062440-T-TATC is described in ClinVar as Benign. ClinVar VariationId is 779520.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.091 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000229329.7. 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
	CMAS	NM_018686.6	MANE Select	c.1114+7_1114+9dupATC		intron	N/A	NP_061156.1	Q8NFW8-1
	CMAS	NR_135117.2		n.1028+7_1028+9dupATC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMAS	ENST00000229329.7	TSL:1 MANE Select	c.1114+6_1114+7insATC		splice_region intron	N/A	ENSP00000229329.2	Q8NFW8-1
	CMAS	ENST00000534981.5	TSL:1	n.*150+6_*150+7insATC		splice_region intron	N/A	ENSP00000446239.1	Q8NFW8-2
	CMAS	ENST00000947440.1		c.1135+6_1135+7insATC		splice_region intron	N/A	ENSP00000617499.1

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 4104 AN: 151744 Hom.: 192 Cov.: 31

Gnomad AFR AF: 0.0935

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000324

Gnomad OTH AF: 0.0201

GnomAD2 exomes AF: 0.00706 AC: 1753 AN: 248334 AF XY: 0.00518

Gnomad AFR exome AF: 0.0946

Gnomad AMR exome AF: 0.00486

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.0000550

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000301

Gnomad OTH exome AF: 0.00395

GnomAD4 exome AF: 0.00277 AC: 4043 AN: 1459238 Hom.: 189 Cov.: 33 AF XY: 0.00235 AC XY: 1706 AN XY: 725912

African (AFR) AF: 0.0956 AC: 3173 AN: 33176

American (AMR) AF: 0.00520 AC: 229 AN: 44062

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39652

South Asian (SAS) AF: 0.000128 AC: 11 AN: 85778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00400 AC: 23 AN: 5756

European-Non Finnish (NFE) AF: 0.000197 AC: 219 AN: 1111078

Other (OTH) AF: 0.00642 AC: 387 AN: 60280

GnomAD4 genome AF: 0.0271 AC: 4112 AN: 151862 Hom.: 193 Cov.: 31 AF XY: 0.0261 AC XY: 1939 AN XY: 74240

African (AFR) AF: 0.0934 AC: 3869 AN: 41408

American (AMR) AF: 0.0116 AC: 177 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.000210 AC: 1 AN: 4772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.000324 AC: 22 AN: 67950

Other (OTH) AF: 0.0199 AC: 42 AN: 2110

Alfa AF: 0.00123 Hom.: 0

Bravo AF: 0.0314

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000415

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
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs140406732; hg19: chr12-22215374;