19-13804875-C-A

Variant names:

• chr19-13804875-C-A
• rs375720071
• NM_001367834.3:c.439C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001367834.3(ZSWIM4):​c.439C>A​(p.Arg147Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R147C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZSWIM4 NM_001367834.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.79
• Publications: 0 publications found

Genes affected

ZSWIM4 (HGNC:25704): (zinc finger SWIM-type containing 4) Predicted to enable zinc ion binding activity. Predicted to be part of Cul2-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.854

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367834.3. 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
	ZSWIM4	NM_001367834.3	MANE Select	c.439C>A	p.Arg147Ser	missense	Exon 3 of 14	NP_001354763.1	K7ERJ6
	ZSWIM4	NM_023072.3		c.439C>A	p.Arg147Ser	missense	Exon 3 of 13	NP_075560.2	Q9H7M6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM4	ENST00000590508.6	TSL:2 MANE Select	c.439C>A	p.Arg147Ser	missense	Exon 3 of 14	ENSP00000468285.2	K7ERJ6
	ZSWIM4	ENST00000938264.1		c.487C>A	p.Arg163Ser	missense	Exon 4 of 15	ENSP00000608323.1
	ZSWIM4	ENST00000938266.1		c.439C>A	p.Arg147Ser	missense	Exon 3 of 14	ENSP00000608325.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.073	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.8
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.030	D
Polyphen		0.99	D
Vest4		0.96
MutPred		0.52		Gain of catalytic residue at S144 (P = 0.0797)
MVP		0.67
MPC		1.2
ClinPred		0.99	D
GERP RS		3.7
Varity_R		0.58
gMVP		0.81
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs375720071; hg19: chr19-13915689;