NM_022900.5:c.25G>C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: CASD1 NM_022900.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.85

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]

ACMG classification

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=0.41787255).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASD1	NM_022900.5	c.25G>C	p.Gly9Arg	missense_variant	Exon 1 of 18	ENST00000297273.9	NP_075051.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASD1	ENST00000297273.9	c.25G>C	p.Gly9Arg	missense_variant	Exon 1 of 18	1	NM_022900.5	ENSP00000297273.4
CASD1	ENST00000447923.5	c.-75+810G>C		intron_variant	Intron 1 of 6	4		ENSP00000396261.1
CASD1	ENST00000417387.1	n.39G>C		non_coding_transcript_exon_variant	Exon 1 of 4	3
CASD1	ENST00000443644.1	n.25G>C		non_coding_transcript_exon_variant	Exon 1 of 6	5		ENSP00000389718.1

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

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: 0.00000187

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.69

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

Other links and lift over

dbSNP: rs888348975; hg19: chr7-94139421;