Genetic Variant NM_018686.6:c.78G>A (chr12-22046381-G-A) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_018686.6(CMAS):c.78G>A(p.Lys26Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000682 in 1,572,908 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00036 ( 0 hom. )

Consequence

CMAS
NM_018686.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.54

Publications

0 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 Gene-Disease associations (from GenCC):

intellectual disability
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

CMAS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 12-22046381-G-A is Benign according to our data. Variant chr12-22046381-G-A is described in ClinVar as [Benign]. Clinvar id is 778585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.54 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMAS	NM_018686.6 link	c.78G>A	p.Lys26Lys	synonymous_variant	Exon 1 of 8	ENST00000229329.7	NP_061156.1	Q8NFW8-1
CMAS	NR_135117.2 link	n.164G>A		non_coding_transcript_exon_variant	Exon 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CMAS	ENST00000229329.7 link	c.78G>A	p.Lys26Lys	synonymous_variant	Exon 1 of 8	1	NM_018686.6	ENSP00000229329.2	Q8NFW8-1
CMAS	ENST00000534981.5 link	n.78G>A		non_coding_transcript_exon_variant	Exon 1 of 7	1		ENSP00000446239.1	Q8NFW8-2
CMAS	ENST00000535610.5 link	n.78G>A		non_coding_transcript_exon_variant	Exon 1 of 5	5		ENSP00000439404.1	F5H296

Frequencies

GnomAD3 genomes

AF:

0.00365

AC:

556

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00222

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000677

AC:

123

AN:

181602

AF XY:

0.000527

show subpopulations

Gnomad AFR exome

AF:

0.0111

Gnomad AMR exome

AF:

0.000526

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000385

Gnomad OTH exome

AF:

0.000430

GnomAD4 exome

AF:

0.000363

AC:

515

AN:

1420584

Hom.:

Cov.:

AF XY:

0.000319

AC XY:

224

AN XY:

702890

show subpopulations

African (AFR)

AF:

0.0131

AC:

419

AN:

31944

American (AMR)

AF:

0.000758

AC:

AN:

38278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25138

East Asian (EAS)

AF:

0.00

AC:

AN:

37238

South Asian (SAS)

AF:

0.0000124

AC:

AN:

80532

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50622

Middle Eastern (MID)

AF:

0.000738

AC:

AN:

5422

European-Non Finnish (NFE)

AF:

0.00000458

AC:

AN:

1092652

Other (OTH)

AF:

0.000970

AC:

AN:

58758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

123

154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00366

AC:

557

AN:

152324

Hom.:

Cov.:

AF XY:

0.00336

AC XY:

250

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0125

AC:

518

AN:

41592

American (AMR)

AF:

0.00222

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

111

139

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00118

Hom.:

Bravo

AF:

0.00437

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 30, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

1.5

PromoterAI

0.028

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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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NM_018686.6:c.78G>A

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