chr20-45883803-G-T

Variant names:

• chr20-45883803-G-T
• rs755076208
• NM_080603.5:c.1211G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080603.5(ZSWIM1):​c.1211G>T​(p.Arg404Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. R404C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZSWIM1 NM_080603.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780
• Publications: 0 publications found

Genes affected

ZSWIM1 (HGNC:16155): (zinc finger SWIM-type containing 1) Predicted to enable zinc ion binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12660891).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080603.5. 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
	ZSWIM1	NM_080603.5	MANE Select	c.1211G>T	p.Arg404Leu	missense	Exon 2 of 2	NP_542170.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM1	ENST00000372523.1	TSL:2 MANE Select	c.1211G>T	p.Arg404Leu	missense	Exon 2 of 2	ENSP00000361601.1	Q9BR11
	ZSWIM1	ENST00000853422.1		c.1211G>T	p.Arg404Leu	missense	Exon 2 of 2	ENSP00000523481.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461196 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726932

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52752

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.078
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.085
Sift	Benign	0.082	T
Sift4G	Benign	0.092	T
Polyphen		0.76	P
Vest4		0.34
MutPred		0.54		Loss of catalytic residue at R404 (P = 0.0267)
MVP		0.072
MPC		0.41
ClinPred		0.13	T
GERP RS		-0.81
Varity_R		0.061
gMVP		0.36
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: rs755076208; hg19: chr20-44512442;