7-94518223-T-C

Position:

• chr7-94518223-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/21 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

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 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASD1	NM_022900.5	c.251T>C	p.Val84Ala	missense_variant	3/18	ENST00000297273.9	NP_075051.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASD1	ENST00000297273.9	c.251T>C	p.Val84Ala	missense_variant	3/18	1	NM_022900.5	ENSP00000297273	P1
CASD1	ENST00000447923.5	c.44T>C	p.Val15Ala	missense_variant	3/7	4		ENSP00000396261
CASD1	ENST00000443644.1	c.133+8006T>C		intron_variant, NMD_transcript_variant		5		ENSP00000389718
CASD1	ENST00000417387.1	n.244+567T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2022

The c.251T>C (p.V84A) alteration is located in exon 3 (coding exon 3) of the CASD1 gene. This alteration results from a T to C substitution at nucleotide position 251, causing the valine (V) at amino acid position 84 to be replaced by an alanine (A). 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	0.061
BayesDel_addAF	Benign	-0.0084	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	18
DANN	Benign	0.83
DEOGEN2	Benign	0.0062	T;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.065
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.074	T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	-0.46	.;N
MutationTaster	Benign	0.98	N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.83	N;N
REVEL	Benign	0.046
Sift	Benign	0.73	T;T
Sift4G	Benign	0.89	T;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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-94147535;