4-48991537-C-G

Variant names:

• chr4-48991537-C-G
• rs1201992070
• NM_025087.3:c.319C>G

Variant summary

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

The NM_025087.3(CWH43):​c.319C>G​(p.Gln107Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CWH43 NM_025087.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.44
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42302626).

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.319C>G	p.Gln107Glu	missense	Exon 3 of 16	NP_079363.2	Q9H720
	CWH43	NM_001286791.2		c.238C>G	p.Gln80Glu	missense	Exon 3 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.319C>G	p.Gln107Glu	missense	Exon 3 of 16	ENSP00000226432.4	Q9H720
	CWH43	ENST00000856986.1		c.319C>G	p.Gln107Glu	missense	Exon 3 of 16	ENSP00000527045.1
	CWH43	ENST00000856987.1		c.319C>G	p.Gln107Glu	missense	Exon 3 of 16	ENSP00000527046.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251400 AF XY: 0.00000736

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461794 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727202

African (AFR) AF: 0.0000896 AC: 3 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111956

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152130 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74318

African (AFR) AF: 0.0000965 AC: 4 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

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	0.090
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Benign	0.59
DEOGEN2	Benign	0.0099	T
Eigen	Benign	-0.099
Eigen_PC	Benign	0.00072
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.4
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.11
Sift	Benign	0.53	T
Sift4G	Benign	0.29	T
Polyphen		0.15	B
Vest4		0.60
MutPred		0.48		Loss of helix (P = 0.0072)
MVP		0.25
MPC		0.089
ClinPred		0.14	T
GERP RS		5.1
Varity_R		0.16
gMVP		0.64
Mutation Taster		=85/15	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

dbSNP: rs1201992070; hg19: chr4-48993554;