Genetic Variant ZSWIM6:p.Gly25del (chr5-61332326-GGGC-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_020928.2(ZSWIM6):c.72_74delCGG(p.Gly25del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000967 in 1,103,948 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000095 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

ZSWIM6
NM_020928.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.17

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:

LOC105378994 (HGNC:):

LOC105378994 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant 5-61332326-GGGC-G is Benign according to our data. Variant chr5-61332326-GGGC-G is described in ClinVar as [Likely_benign]. Clinvar id is 1636008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM6	NM_020928.2 link	c.72_74delCGG	p.Gly25del	disruptive_inframe_deletion	Exon 1 of 14	ENST00000252744.6	NP_065979.1	Q9HCJ5
LOC105378994	XR_007058781.1 link	n.-113_-111delGCC		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSWIM6	ENST00000252744.6 link	c.72_74delCGG	p.Gly25del	disruptive_inframe_deletion	Exon 1 of 14	5	NM_020928.2	ENSP00000252744.5		Q9HCJ5

Frequencies

GnomAD3 genomes

AF:

0.0000946

AC:

AN:

148036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000673

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000900

Gnomad OTH

AF:

0.000493

GnomAD3 exomes

AF:

0.00658

AC:

AN:

456

Hom.:

AF XY:

0.00685

AC XY:

AN XY:

292

show subpopulations

Gnomad ASJ exome

AF:

0.00

Gnomad FIN exome

AF:

0.0138

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00110

AC:

1053

AN:

955816

Hom.:

AF XY:

0.00130

AC XY:

587

AN XY:

451164

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.00447

Gnomad4 ASJ exome

AF:

0.00290

Gnomad4 EAS exome

AF:

0.00593

Gnomad4 SAS exome

AF:

0.000548

Gnomad4 FIN exome

AF:

0.00606

Gnomad4 NFE exome

AF:

0.000843

Gnomad4 OTH exome

AF:

0.00182

GnomAD4 genome

AF:

0.0000945

AC:

AN:

148132

Hom.:

Cov.:

AF XY:

0.0000969

AC XY:

AN XY:

72240

show subpopulations

Gnomad4 AFR

AF:

0.000122

Gnomad4 AMR

AF:

0.0000673

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000900

Gnomad4 OTH

AF:

0.000487

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

May 04, 2022

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

ZSWIM6-related disorder

Benign:1

Dec 22, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

5-61332326-GGGCGGCGGCGGC-GGGCGGCGGC

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