chr19-13799856-G-T

Position:

• chr19-13799856-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001367834.3(ZSWIM4):​c.290G>T​(p.Arg97Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZSWIM4 NM_001367834.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.88

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]

ZSWIM4 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSWIM4	NM_001367834.3	c.290G>T	p.Arg97Leu	missense_variant	2/14	ENST00000590508.6	NP_001354763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZSWIM4	ENST00000590508.6	c.290G>T	p.Arg97Leu	missense_variant	2/14	2	NM_001367834.3	ENSP00000468285.2
ZSWIM4	ENST00000254323.6	c.290G>T	p.Arg97Leu	missense_variant	2/13	2		ENSP00000254323.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

Mar 19, 2024

The c.290G>T (p.R97L) alteration is located in exon 2 (coding exon 2) of the ZSWIM4 gene. This alteration results from a G to T substitution at nucleotide position 290, causing the arginine (R) at amino acid position 97 to be replaced by a leucine (L). 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	0.20
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.13
Sift	Benign	0.032	D
Sift4G	Benign	0.19	T
Polyphen		0.95	P
Vest4		0.61
MutPred		0.40		Loss of disorder (P = 0.0325);
MVP		0.62
MPC		1.3
ClinPred		0.90	D
GERP RS		4.4
Varity_R		0.16
gMVP		0.76

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

LitVar

Other links and lift over

dbSNP: rs376618899; hg19: chr19-13910670;