Variant 12-22055532-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_018686.6(CMAS):c.481A>G(p.Ile161Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CMAS
NM_018686.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.31

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34534246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMAS	NM_018686.6 linkuse as main transcript	c.481A>G	p.Ile161Val	missense_variant	3/8	ENST00000229329.7	NP_061156.1
CMAS	NR_135117.2 linkuse as main transcript	n.567A>G		non_coding_transcript_exon_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMAS	ENST00000229329.7 linkuse as main transcript	c.481A>G	p.Ile161Val	missense_variant	3/8	1	NM_018686.6	ENSP00000229329	P1	Q8NFW8-1
CMAS	ENST00000534981.5 linkuse as main transcript	c.481A>G	p.Ile161Val	missense_variant, NMD_transcript_variant	3/7	1		ENSP00000446239		Q8NFW8-2
CMAS	ENST00000538498.1 linkuse as main transcript	c.4A>G	p.Ile2Val	missense_variant	2/4	3		ENSP00000440605
CMAS	ENST00000535610.5 linkuse as main transcript	c.*71A>G		3_prime_UTR_variant, NMD_transcript_variant	2/5	5		ENSP00000439404

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460324

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726328

show subpopulations

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:

0.00000180

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

Dec 17, 2023

The c.481A>G (p.I161V) alteration is located in exon 3 (coding exon 3) of the CMAS gene. This alteration results from a A to G substitution at nucleotide position 481, causing the isoleucine (I) at amino acid position 161 to be replaced by a valine (V). 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

0.20

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.069

T;.

Eigen

Benign

0.19

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-0.50

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.65

N;N

REVEL

Benign

0.13

Sift

Benign

0.073

T;D

Sift4G

Benign

0.36

T;T

Polyphen

0.027

B;.

Vest4

0.39

MutPred

0.52

Gain of disorder (P = 0.1167);.;

MVP

0.36

MPC

0.95

ClinPred

0.84

GERP RS

5.7

Varity_R

0.13

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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