20-45877379-C-A

Variant names:

• chr20-45877379-C-A
• NM_080752.4:c.821C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_080752.4(ZSWIM3):​c.821C>A​(p.Ser274Tyr) 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: 3.32

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31844312).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM3	NM_080752.4	c.821C>A	p.Ser274Tyr	missense_variant	Exon 2 of 2	ENST00000255152.3	NP_542790.2
ZSWIM3	NR_037628.2	n.1188C>A		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.821C>A	p.Ser274Tyr	missense_variant	Exon 2 of 2	1	NM_080752.4	ENSP00000255152.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 83

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.821C>A (p.S274Y) alteration is located in exon 2 (coding exon 2) of the ZSWIM3 gene. This alteration results from a C to A substitution at nucleotide position 821, causing the serine (S) at amino acid position 274 to be replaced by a tyrosine (Y). 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	0.15
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.11
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.037	D
Polyphen		0.90	P
Vest4		0.35
MutPred		0.39		Gain of phosphorylation at S274 (P = 0.0772);
MVP		0.28
MPC		0.99
ClinPred		0.90	D
GERP RS		4.5
Varity_R		0.14
gMVP		0.34

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: chr20-44506018;