4-49061855-C-T

Variant names:

• chr4-49061855-C-T
• rs1051447
• NM_025087.3:c.2065C>T

Variant summary

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

The NM_025087.3(CWH43):​c.2065C>T​(p.His689Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000163 in 1,225,882 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: CWH43 NM_025087.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.07
• 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CWH43	NM_025087.3	c.2065C>T	p.His689Tyr	missense_variant	Exon 16 of 16	ENST00000226432.9	NP_079363.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CWH43	ENST00000226432.9	c.2065C>T	p.His689Tyr	missense_variant	Exon 16 of 16	1	NM_025087.3	ENSP00000226432.4
CWH43	ENST00000513409.1	c.1984C>T	p.His662Tyr	missense_variant	Exon 16 of 16	2		ENSP00000422802.1
CWH43	ENST00000514053.6	n.*1075C>T		non_coding_transcript_exon_variant	Exon 14 of 14	5		ENSP00000425157.2
CWH43	ENST00000514053.6	n.*1075C>T		3_prime_UTR_variant	Exon 14 of 14	5		ENSP00000425157.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000163 AC: 2 AN: 1225882 Hom.: 0 Cov.: 27 AF XY: 0.00000165 AC XY: 1 AN XY: 605934

African (AFR) AF: 0.00 AC: 0 AN: 26346

American (AMR) AF: 0.00 AC: 0 AN: 18376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20044

East Asian (EAS) AF: 0.00 AC: 0 AN: 31472

South Asian (SAS) AF: 0.00 AC: 0 AN: 63662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4928

European-Non Finnish (NFE) AF: 0.00000206 AC: 2 AN: 970014

Other (OTH) AF: 0.00 AC: 0 AN: 49808

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	26
DANN	Benign	0.97
DEOGEN2	Benign	0.0012	T;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.0060	T
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.4	L;.
PhyloP100		4.1
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.42	N;N
REVEL	Benign	0.14
Sift	Benign	0.93	T;T
Sift4G	Uncertain	0.0070	D;D
Polyphen		1.0	D;.
Vest4		0.51
MutPred		0.35		Gain of glycosylation at Y684 (P = 0.0046);.;
MVP		0.49
MPC		0.26
ClinPred		0.94	D
GERP RS		4.6
Varity_R		0.10
gMVP		0.47
Mutation Taster		=96/4	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: rs1051447; hg19: chr4-49063872;