NM_001367834.3:c.92G>C

Variant names:

• chr19-13795740-G-C
• rs1484828467
• NM_001367834.3:c.92G>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001367834.3(ZSWIM4):​c.92G>C​(p.Arg31Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 1,224,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R31G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: ZSWIM4 NM_001367834.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.15
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.30854636).

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.92G>C	p.Arg31Pro	missense	Exon 1 of 14	NP_001354763.1	K7ERJ6
	ZSWIM4	NM_023072.3		c.92G>C	p.Arg31Pro	missense	Exon 1 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.92G>C	p.Arg31Pro	missense	Exon 1 of 14	ENSP00000468285.2	K7ERJ6
	ZSWIM4	ENST00000938264.1		c.92G>C	p.Arg31Pro	missense	Exon 1 of 15	ENSP00000608323.1
	ZSWIM4	ENST00000938266.1		c.92G>C	p.Arg31Pro	missense	Exon 1 of 14	ENSP00000608325.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151424 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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

GnomAD4 exome AF: 0.0000121 AC: 13 AN: 1073356 Hom.: 0 Cov.: 30 AF XY: 0.00000985 AC XY: 5 AN XY: 507388

African (AFR) AF: 0.00 AC: 0 AN: 22882

American (AMR) AF: 0.00107 AC: 9 AN: 8398

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13800

East Asian (EAS) AF: 0.0000379 AC: 1 AN: 26404

South Asian (SAS) AF: 0.0000500 AC: 1 AN: 19996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2962

European-Non Finnish (NFE) AF: 0.00000109 AC: 1 AN: 915036

Other (OTH) AF: 0.0000233 AC: 1 AN: 42932

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151532 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74058

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.000131 AC: 2 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5114

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67706

Other (OTH) AF: 0.00 AC: 0 AN: 2098

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

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	0.12
BayesDel_addAF	Benign	0.0057	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.063
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.70	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.2
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.17
Sift	Benign	0.035	D
Sift4G	Benign	0.067	T
Polyphen		0.96	D
Vest4		0.30
MutPred		0.31		Loss of MoRF binding (P = 0.003)
MVP		0.53
MPC		0.86
ClinPred		0.81	D
GERP RS		3.7
PromoterAI		0.0091	Neutral
Varity_R		0.38
gMVP		0.36
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: rs1484828467; hg19: chr19-13906554;