rs188271074

Variant names:

• chr1-45018522-C-A
• rs188271074
• NM_020883.2:c.3490G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-45018522-C-A
• chr1-45018522-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020883.2(ZSWIM5):​c.3490G>T​(p.Asp1164Tyr) variant causes a missense change involving the alteration of a 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. D1164N) 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: 7.57

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.842

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM5	NM_020883.2	c.3490G>T	p.Asp1164Tyr	missense_variant	Exon 14 of 14	ENST00000359600.6	NP_065934.1
ZSWIM5	XM_047426192.1	c.3313G>T	p.Asp1105Tyr	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.3490G>T	p.Asp1164Tyr	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	0.94
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.88
MVP		0.77
MPC		0.50
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.86
gMVP		0.69

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: rs188271074; hg19: chr1-45484194;