12-22065215-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_018686.6(CMAS):c.1209C>T(p.Tyr403Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 1,614,060 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 17 hom. )

Consequence

CMAS
NM_018686.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.426

Publications

7 publications found

Variant links:

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 links:

ST8SIA1 (HGNC:10869): (ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1) Gangliosides are membrane-bound glycosphingolipids containing sialic acid. Ganglioside GD3 is known to be important for cell adhesion and growth of cultured malignant cells. The protein encoded by this gene is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to GM3 to produce gangliosides GD3 and GT3. The encoded protein may be found in the Golgi apparatus and is a member of glycosyltransferase family 29. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2015]

ST8SIA1 links:

LOC105369690 (HGNC:):

LOC105369690 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 12-22065215-C-T is Benign according to our data. Variant chr12-22065215-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 790461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.426 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMAS	NM_018686.6 link	c.1209C>T	p.Tyr403Tyr	synonymous_variant	Exon 8 of 8	ENST00000229329.7	NP_061156.1	Q8NFW8-1
CMAS	NR_135117.2 link	n.1123C>T		non_coding_transcript_exon_variant	Exon 7 of 7
LOC105369690	XR_931423.4 link	n.445+1130G>A		intron_variant	Intron 4 of 4
LOC105369690	XR_931424.4 link	n.1459+1130G>A		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CMAS	ENST00000229329.7 link	c.1209C>T	p.Tyr403Tyr	synonymous_variant	Exon 8 of 8	1	NM_018686.6	ENSP00000229329.2	Q8NFW8-1
CMAS	ENST00000534981.5 link	n.*245C>T		non_coding_transcript_exon_variant	Exon 7 of 7	1		ENSP00000446239.1	Q8NFW8-2
CMAS	ENST00000534981.5 link	n.*245C>T		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000446239.1	Q8NFW8-2
ST8SIA1	ENST00000536535.1 link	n.291+1130G>A		intron_variant	Intron 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.00283

AC:

430

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00437

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00344

AC:

866

AN:

251420

AF XY:

0.00369

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00275

Gnomad ASJ exome

AF:

0.0122

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.00504

Gnomad OTH exome

AF:

0.00701

GnomAD4 exome

AF:

0.00376

AC:

5493

AN:

1461792

Hom.:

Cov.:

AF XY:

0.00379

AC XY:

2757

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.000388

AC:

AN:

33480

American (AMR)

AF:

0.00271

AC:

121

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0117

AC:

305

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.000707

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.000842

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00381

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00419

AC:

4660

AN:

1111934

Other (OTH)

AF:

0.00440

AC:

266

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

276

552

829

1105

1381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00282

AC:

429

AN:

152268

Hom.:

Cov.:

AF XY:

0.00258

AC XY:

192

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.000722

AC:

AN:

41552

American (AMR)

AF:

0.00203

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0115

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00166

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.000471

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00435

AC:

296

AN:

68028

Other (OTH)

AF:

0.00426

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00424

Hom.:

Bravo

AF:

0.00298

EpiCase

AF:

0.00573

EpiControl

AF:

0.00693

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Oct 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CMAS: BP4, BP7, BS2 -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

1.9

(source)

DANN

Benign

0.81

PhyloP100

-0.43

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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12-22065215-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over