chr20-45883319-C-T

Variant summary

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

The NM_080603.5(ZSWIM1):​c.727C>T​(p.His243Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,790 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZSWIM1
NM_080603.5 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.37
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZSWIM1NM_080603.5 linkc.727C>T p.His243Tyr missense_variant Exon 2 of 2 ENST00000372523.1 NP_542170.3 Q9BR11
ZSWIM1XM_005260610.6 linkc.727C>T p.His243Tyr missense_variant Exon 2 of 2 XP_005260667.1 Q9BR11
ZSWIM1XM_005260611.5 linkc.727C>T p.His243Tyr missense_variant Exon 2 of 2 XP_005260668.1 Q9BR11
ZSWIM1XM_011529100.3 linkc.727C>T p.His243Tyr missense_variant Exon 2 of 2 XP_011527402.1 Q9BR11

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZSWIM1ENST00000372523.1 linkc.727C>T p.His243Tyr missense_variant Exon 2 of 2 2 NM_080603.5 ENSP00000361601.1 Q9BR11

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251166
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135826
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461790
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 21, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.727C>T (p.H243Y) alteration is located in exon 2 (coding exon 1) of the ZSWIM1 gene. This alteration results from a C to T substitution at nucleotide position 727, causing the histidine (H) at amino acid position 243 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
0.24
BayesDel_addAF
Benign
-0.044
T
BayesDel_noAF
Benign
-0.29
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
T;T
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.56
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.67
.;T
M_CAP
Benign
0.0056
T
MetaRNN
Uncertain
0.54
D;D
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.1
L;L
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-0.96
N;N
REVEL
Benign
0.18
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.62
MutPred
0.46
Gain of catalytic residue at H243 (P = 0.0519);Gain of catalytic residue at H243 (P = 0.0519);
MVP
0.17
MPC
0.40
ClinPred
0.37
T
GERP RS
5.3
Varity_R
0.52
gMVP
0.46

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs778497195; hg19: chr20-44511958; API