7-94510109-G-C

Variant names:

• chr7-94510109-G-C
• rs888348975
• NM_022900.5:c.25G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022900.5(CASD1):​c.25G>C​(p.Gly9Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000145 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G9S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: CASD1 NM_022900.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.85
• Publications: 1 publications found

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]

ENSG00000309657 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41787255).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022900.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASD1	NM_022900.5	MANE Select	c.25G>C	p.Gly9Arg	missense	Exon 1 of 18	NP_075051.4
	CASD1	NM_001363426.1		c.-598G>C		5_prime_UTR	Exon 1 of 19	NP_001350355.1
	CASD1	NM_001363428.1		c.-547G>C		5_prime_UTR	Exon 1 of 18	NP_001350357.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASD1	ENST00000297273.9	TSL:1 MANE Select	c.25G>C	p.Gly9Arg	missense	Exon 1 of 18	ENSP00000297273.4	Q96PB1
	CASD1	ENST00000919855.1		c.25G>C	p.Gly9Arg	missense	Exon 1 of 18	ENSP00000589914.1
	CASD1	ENST00000919856.1		c.25G>C	p.Gly9Arg	missense	Exon 1 of 17	ENSP00000589915.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1377936 Hom.: 0 Cov.: 32 AF XY: 0.00000147 AC XY: 1 AN XY: 679574

African (AFR) AF: 0.00 AC: 0 AN: 29500

American (AMR) AF: 0.00 AC: 0 AN: 33452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24628

East Asian (EAS) AF: 0.00 AC: 0 AN: 34038

South Asian (SAS) AF: 0.00 AC: 0 AN: 76870

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4194

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1069220

Other (OTH) AF: 0.00 AC: 0 AN: 56910

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.00040	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.017	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Benign	0.28	N
LIST_S2	Uncertain	0.93	D
M_CAP	Pathogenic	0.76	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.0	L
PhyloP100		5.9
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.19
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.041	D
Polyphen		1.0	D
Vest4		0.35
MutPred		0.35		Gain of MoRF binding (P = 0.0127)
MVP		0.36
MPC		1.3
ClinPred		0.97	D
GERP RS		3.5
PromoterAI		0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.69
Mutation Taster		=47/53	disease causing

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

Other links and lift over

dbSNP: rs888348975; hg19: chr7-94139421;