Variant 5-61332326-G-GGGCGGCGGC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_020928.2(ZSWIM6):c.66_74dupCGGCGGCGG(p.Gly23_Gly25dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 148,044 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZSWIM6
NM_020928.2 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.671

Variant links:

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]

ZSWIM6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSWIM6	NM_020928.2 link	c.66_74dupCGGCGGCGG	p.Gly23_Gly25dup	disruptive_inframe_insertion	1/14	ENST00000252744.6	NP_065979.1	Q9HCJ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZSWIM6	ENST00000252744.6 link	c.66_74dupCGGCGGCGG	p.Gly23_Gly25dup	disruptive_inframe_insertion	1/14	5	NM_020928.2	ENSP00000252744.5		Q9HCJ5

Frequencies

GnomAD3 genomes

AF:

0.000135

AC:

AN:

148044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000366

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000202

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000984

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000825

AC:

AN:

969396

Hom.:

Cov.:

AF XY:

0.0000131

AC XY:

AN XY:

457600

show subpopulations

Gnomad4 AFR exome

AF:

0.000254

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:

0.00000237

Gnomad4 OTH exome

AF:

0.0000276

GnomAD4 genome

AF:

0.000135

AC:

AN:

148044

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

AN XY:

72140

show subpopulations

Gnomad4 AFR

AF:

0.000366

Gnomad4 AMR

AF:

0.000202

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000984

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 19, 2022	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. This variant has not been reported in the literature in individuals affected with ZSWIM6-related conditions. This variant, c.66_74dup, results in the insertion of 3 amino acid(s) of the ZSWIM6 protein (p.Gly24_Gly26dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). -
Uncertain significance, criteria provided, single submitter	clinical testing	GeneDx	May 29, 2024	Not observed at significant frequency in large population cohorts (gnomAD); In-frame insertion of three amino acid in a repetitive region with no known function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over