Variant 7-94510214-C-G 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_022900.5(CASD1):c.130C>G(p.Arg44Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000222 in 1,351,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

CASD1
NM_022900.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.32

Variant links:

Genes affected

CASD1 (HGNC:16014): (CAS1 domain containing 1) Enables N-acetylneuraminate 7-O(or 9-O)-acetyltransferase activity. Involved in carbohydrate metabolic process. Is integral component of Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

CASD1 links:

CASD1 (HGNC:):

CASD1 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=0.1493392).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASD1	NM_022900.5 linkuse as main transcript	c.130C>G	p.Arg44Gly	missense_variant	1/18	ENST00000297273.9	NP_075051.4	Q96PB1Q8WZ77

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CASD1	ENST00000297273.9 linkuse as main transcript	c.130C>G	p.Arg44Gly	missense_variant	1/18	1	NM_022900.5	ENSP00000297273.4	Q96PB1
CASD1	ENST00000447923.5 linkuse as main transcript	c.-75+915C>G		intron_variant		4		ENSP00000396261.1	C9JDR3
CASD1	ENST00000417387.1 linkuse as main transcript	n.144C>G		non_coding_transcript_exon_variant	1/4	3
CASD1	ENST00000443644.1 linkuse as main transcript	n.130C>G		non_coding_transcript_exon_variant	1/6	5		ENSP00000389718.1	F8WDQ7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000844

AC:

AN:

118416

Hom.:

AF XY:

0.00

AC XY:

AN XY:

63440

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000519

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000222

AC:

AN:

1351932

Hom.:

Cov.:

AF XY:

0.00000300

AC XY:

AN XY:

666262

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000319

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000319

Gnomad4 SAS exome

AF:

0.0000134

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Nov 20, 2024

The c.130C>G (p.R44G) alteration is located in exon 1 (coding exon 1) of the CASD1 gene. This alteration results from a C to G substitution at nucleotide position 130, causing the arginine (R) at amino acid position 44 to be replaced by a glycine (G). 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

0.081

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.012

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.85

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.51

MutationAssessor

Benign

-1.1

PrimateAI

Uncertain

0.79

PROVEAN

Benign

0.070

REVEL

Benign

0.21

Sift

Benign

0.24

Sift4G

Benign

0.61

Polyphen

0.0

Vest4

0.090

MutPred

0.42

Loss of methylation at R44 (P = 0.0385);

MVP

0.32

MPC

0.50

ClinPred

0.20

GERP RS

2.6

Varity_R

0.27

gMVP

0.51

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over