NM_080752.4:c.565A>T

Variant names:

• chr20-45877123-A-T
• rs766739475
• NM_080752.4:c.565A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080752.4(ZSWIM3):​c.565A>T​(p.Met189Leu) 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. 16/22 in silico tools predict a benign 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. M189V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZSWIM3 NM_080752.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054347783).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080752.4. 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
	ZSWIM3	NM_080752.4	MANE Select	c.565A>T	p.Met189Leu	missense	Exon 2 of 2	NP_542790.2	Q96MP5
	ZSWIM3	NR_037628.2		n.932A>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM3	ENST00000255152.3	TSL:1 MANE Select	c.565A>T	p.Met189Leu	missense	Exon 2 of 2	ENSP00000255152.2	Q96MP5
	ZSWIM3	ENST00000926005.1		c.484A>T	p.Met162Leu	missense	Exon 2 of 2	ENSP00000596064.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.88
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.046
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.1
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.17
Sift	Benign	0.61	T
Sift4G	Benign	0.82	T
Polyphen		0.0020	B
Vest4		0.18
MutPred		0.30		Gain of sheet (P = 0.0827)
MVP		0.067
MPC		0.26
ClinPred		0.60	D
GERP RS		4.4
Varity_R		0.10
gMVP		0.37
Mutation Taster		=96/4	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: rs766739475; hg19: chr20-44505762;