4-48998483-C-T

Variant names:

• chr4-48998483-C-T
• NM_025087.3:c.737C>T

Variant summary

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

The NM_025087.3(CWH43):​c.737C>T​(p.Ala246Val) 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. 15/24 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: CWH43 NM_025087.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.632
• Publications: 0 publications found

Genes affected

CWH43 (HGNC:26133): (cell wall biogenesis 43 C-terminal homolog) Predicted to be involved in GPI anchor biosynthetic process. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025087.3. 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
	CWH43	NM_025087.3	MANE Select	c.737C>T	p.Ala246Val	missense	Exon 6 of 16	NP_079363.2	Q9H720
	CWH43	NM_001286791.2		c.656C>T	p.Ala219Val	missense	Exon 6 of 16	NP_001273720.1	E7EQL2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CWH43	ENST00000226432.9	TSL:1 MANE Select	c.737C>T	p.Ala246Val	missense	Exon 6 of 16	ENSP00000226432.4	Q9H720
	CWH43	ENST00000856986.1		c.737C>T	p.Ala246Val	missense	Exon 6 of 16	ENSP00000527045.1
	CWH43	ENST00000856987.1		c.737C>T	p.Ala246Val	missense	Exon 6 of 16	ENSP00000527046.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	0.095
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.63
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.045
Sift	Benign	0.28	T
Sift4G	Benign	0.37	T
Polyphen		0.0030	B
Vest4		0.18
MutPred		0.49		Loss of glycosylation at S247 (P = 0.0224)
MVP		0.13
MPC		0.053
ClinPred		0.10	T
GERP RS		1.2
Varity_R		0.067
gMVP		0.76
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.32		Position offset: -23

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr4-49000500;