chr1-45034320-G-C

Position:

• chr1-45034320-G-C

Variant summary

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

The ENST00000359600.6(ZSWIM5):​c.2441C>G​(p.Ala814Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZSWIM5 ENST00000359600.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.72

Genes affected

ZSWIM5 (HGNC:29299): (zinc finger SWIM-type containing 5) Predicted to enable zinc ion binding activity. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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/exons	MANE	Protein	UniProt
ZSWIM5	NM_020883.2	c.2441C>G	p.Ala814Gly	missense_variant	11/14	ENST00000359600.6	NP_065934.1
ZSWIM5	XM_047426192.1	c.2264C>G	p.Ala755Gly	missense_variant	10/13		XP_047282148.1
ZSWIM5	XM_011541861.4	c.*208C>G		3_prime_UTR_variant	11/11		XP_011540163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZSWIM5	ENST00000359600.6	c.2441C>G	p.Ala814Gly	missense_variant	11/14	1	NM_020883.2	ENSP00000352614	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 12, 2023

The c.2441C>G (p.A814G) alteration is located in exon 11 (coding exon 11) of the ZSWIM5 gene. This alteration results from a C to G substitution at nucleotide position 2441, causing the alanine (A) at amino acid position 814 to be replaced by a glycine (G). 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	0.49
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.25
Sift	Benign	0.044	D
Sift4G	Benign	0.064	T
Polyphen		0.84	P
Vest4		0.71
MutPred		0.36		Loss of helix (P = 0.0626);
MVP		0.59
MPC		0.40
ClinPred		0.98	D
GERP RS		4.4
Varity_R		0.58
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr1-45499992;