chr5-61332285-G-A

Variant names:

• chr5-61332285-G-A
• rs1744263511
• NM_020928.2:c.13G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020928.2(ZSWIM6):​c.13G>A​(p.Gly5Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000394 in 1,014,170 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000039 (0 hom.)
• Consequence: ZSWIM6 NM_020928.2 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 5.75

Genes affected

ZSWIM6 (HGNC:29316): (zinc finger SWIM-type containing 6) The protein encoded by this gene contains a zinc finger SWI2/SNF2 and MuDR (SWIM) domain. Proteins with SWIM domains have been found in a diverse number of species and are predicted to interact with DNA or proteins. Mutations in this gene result in acromelic frontonasal dysostosis. [provided by RefSeq, Apr 2017]

LOC105378994 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09601331).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM6	NM_020928.2	c.13G>A	p.Gly5Arg	missense_variant	Exon 1 of 14	ENST00000252744.6	NP_065979.1
LOC105378994	XR_007058781.1	n.-69C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSWIM6	ENST00000252744.6	c.13G>A	p.Gly5Arg	missense_variant	Exon 1 of 14	5	NM_020928.2	ENSP00000252744.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000394 AC: 4 AN: 1014170 Hom.: 0 Cov.: 28 AF XY: 0.00000627 AC XY: 3 AN XY: 478280

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: 0.000105

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000114

Gnomad4 OTH exome AF: 0.0000257

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Acromelic frontonasal dysostosis;C4693405:Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features Uncertain:1

-

Juno Genomics, Hangzhou Juno Genomics, Inc

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PM2_Supporting+PS2_Supporting+PP4+BP4 -

not provided Uncertain:1

Aug 12, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 5 of the ZSWIM6 protein (p.Gly5Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ZSWIM6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1490982). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Uncertain	24
DANN	Benign	0.90
DEOGEN2	Benign	0.00027	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.85	D
M_CAP	Pathogenic	0.51	D
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.14
Sift	Benign	0.098	T
Sift4G	Benign	0.19	T
Polyphen		0.0010	B
Vest4		0.14
MutPred		0.21		Gain of MoRF binding (P = 0.0228);
MVP		0.014
MPC		0.59
ClinPred		0.20	T
GERP RS		-0.53
Varity_R		0.057
gMVP		0.37

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

Other links and lift over

dbSNP: rs1744263511; hg19: chr5-60628112;