NM_080752.4:c.270A>T

Variant names:

• chr20-45876828-A-T
• NM_080752.4:c.270A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080752.4(ZSWIM3):​c.270A>T​(p.Arg90Ser) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZSWIM3 NM_080752.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0560

Genes affected

ZSWIM3 (HGNC:16157): (zinc finger SWIM-type containing 3) Predicted to enable zinc ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24162343).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM3	NM_080752.4	c.270A>T	p.Arg90Ser	missense_variant	Exon 2 of 2	ENST00000255152.3	NP_542790.2
ZSWIM3	NR_037628.2	n.637A>T		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSWIM3	ENST00000255152.3	c.270A>T	p.Arg90Ser	missense_variant	Exon 2 of 2	1	NM_080752.4	ENSP00000255152.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.270A>T (p.R90S) alteration is located in exon 2 (coding exon 2) of the ZSWIM3 gene. This alteration results from a A to T substitution at nucleotide position 270, causing the arginine (R) at amino acid position 90 to be replaced by a serine (S). 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	Uncertain	0.43
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.24
Sift	Benign	0.052	T
Sift4G	Uncertain	0.015	D
Polyphen		0.97	D
Vest4		0.44
MutPred		0.31		Gain of helix (P = 0.062);
MVP		0.35
MPC		0.66
ClinPred		0.74	D
GERP RS		1.9
Varity_R		0.096
gMVP		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-44505467;