Variant 7-94510109-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_022900.5(CASD1):c.25G>A(p.Gly9Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000363 in 1,377,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

CASD1
NM_022900.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.85

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:

Genome browser will be placed here

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=0.34538484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASD1	NM_022900.5 linkuse as main transcript	c.25G>A	p.Gly9Ser	missense_variant	1/18	ENST00000297273.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CASD1	ENST00000297273.9 linkuse as main transcript	c.25G>A	p.Gly9Ser	missense_variant	1/18	1	NM_022900.5	P1
CASD1	ENST00000447923.5 linkuse as main transcript	c.-75+810G>A		intron_variant		4
CASD1	ENST00000417387.1 linkuse as main transcript	n.39G>A		non_coding_transcript_exon_variant	1/4	3
CASD1	ENST00000443644.1 linkuse as main transcript	c.25G>A	p.Gly9Ser	missense_variant, NMD_transcript_variant	1/6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000714

AC:

AN:

140006

Hom.:

AF XY:

0.00

AC XY:

AN XY:

74202

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000187

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000363

AC:

AN:

1377936

Hom.:

Cov.:

AF XY:

0.00000589

AC XY:

AN XY:

679574

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000294

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000374

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 28, 2022

The c.25G>A (p.G9S) alteration is located in exon 1 (coding exon 1) of the CASD1 gene. This alteration results from a G to A substitution at nucleotide position 25, causing the glycine (G) at amino acid position 9 to be replaced by a serine (S). 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

Pathogenic

0.79

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.32

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.014

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.78

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.35

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.0

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

0.20

REVEL

Benign

0.24

Sift

Benign

0.15

Sift4G

Benign

0.24

Polyphen

1.0

Vest4

0.34

MutPred

0.37

Loss of helix (P = 0.0376);

MVP

0.43

MPC

1.2

ClinPred

0.80

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.53

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