rs376021528

Variant names:

• chr1-45019184-C-G
• rs376021528
• NM_020883.2:c.2828G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-45019184-C-G
• chr1-45019184-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020883.2(ZSWIM5):​c.2828G>C​(p.Arg943Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. R943Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZSWIM5 NM_020883.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82

Genes affected

ZSWIM5 (HGNC:29299): (zinc finger SWIM-type containing 5) Predicted to enable zinc ion binding activity. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.772

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM5	NM_020883.2	c.2828G>C	p.Arg943Pro	missense_variant	Exon 14 of 14	ENST00000359600.6	NP_065934.1
ZSWIM5	XM_047426192.1	c.2651G>C	p.Arg884Pro	missense_variant	Exon 13 of 13		XP_047282148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSWIM5	ENST00000359600.6	c.2828G>C	p.Arg943Pro	missense_variant	Exon 14 of 14	1	NM_020883.2	ENSP00000352614.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.6	L
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.029	D
Polyphen		0.98	D
Vest4		0.72
MutPred		0.39		Gain of loop (P = 0.0045);
MVP		0.73
MPC		0.59
ClinPred		0.97	D
GERP RS		4.7
Varity_R		0.82
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs376021528; hg19: chr1-45484856;