Variant 12-22046356-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018686.6(CMAS):c.53G>T(p.Arg18Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CMAS
NM_018686.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.01

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20908764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CMAS	NM_018686.6 linkuse as main transcript	c.53G>T	p.Arg18Leu	missense_variant	1/8	ENST00000229329.7
CMAS	NR_135117.2 linkuse as main transcript	n.139G>T		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CMAS	ENST00000229329.7 linkuse as main transcript	c.53G>T	p.Arg18Leu	missense_variant	1/8	1	NM_018686.6	P1	Q8NFW8-1
CMAS	ENST00000534981.5 linkuse as main transcript	c.53G>T	p.Arg18Leu	missense_variant, NMD_transcript_variant	1/7	1			Q8NFW8-2
CMAS	ENST00000535610.5 linkuse as main transcript	c.53G>T	p.Arg18Leu	missense_variant, NMD_transcript_variant	1/5	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1377838

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

677874

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The c.53G>T (p.R18L) alteration is located in exon 1 (coding exon 1) of the CMAS gene. This alteration results from a G to T substitution at nucleotide position 53, causing the arginine (R) at amino acid position 18 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.0076

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.051

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.81

M_CAP

Pathogenic

0.66

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.90

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.40

REVEL

Benign

0.15

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.34

MutPred

0.32

Loss of methylation at R18 (P = 0.0132);

MVP

0.35

MPC

1.8

ClinPred

0.62

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.29

gMVP

0.52

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over