7-94518223-T-C

Variant names:

• chr7-94518223-T-C
• NM_022900.5:c.251T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022900.5(CASD1):​c.251T>C​(p.Val84Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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)
• Consequence: CASD1 NM_022900.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.25
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07412693).

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.251T>C	p.Val84Ala	missense	Exon 3 of 18	NP_075051.4
	CASD1	NM_001363426.1		c.-372T>C		5_prime_UTR	Exon 3 of 19	NP_001350355.1
	CASD1	NM_001363428.1		c.-321T>C		5_prime_UTR	Exon 3 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.251T>C	p.Val84Ala	missense	Exon 3 of 18	ENSP00000297273.4	Q96PB1
	CASD1	ENST00000919855.1		c.251T>C	p.Val84Ala	missense	Exon 3 of 18	ENSP00000589914.1
	CASD1	ENST00000919856.1		c.251T>C	p.Val84Ala	missense	Exon 3 of 17	ENSP00000589915.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

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	Benign	0.061
BayesDel_addAF	Benign	-0.0084	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	18
DANN	Benign	0.83
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.065
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	-0.46	N
PhyloP100		2.2
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.83	N
REVEL	Benign	0.046
Sift	Benign	0.73	T
Sift4G	Benign	0.89	T
Polyphen		0.0	B
Vest4		0.097
MutPred		0.30		Loss of stability (P = 0.0254)
MVP		0.44
MPC		0.46
ClinPred		0.20	T
GERP RS		5.5
Varity_R		0.046
gMVP		0.24
Mutation Taster		=81/19	polymorphism

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

hg19: chr7-94147535;