chr5-61332326-G-GGGCGGC

Position:

• chr5-61332326-G-GGGCGGC

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_020928.2(ZSWIM6):​c.69_74dup​(p.Gly25_Gly26dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000568 in 1,117,528 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P18P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00076 (0 hom., cov: 26)
  • Exomes 𝑓: 0.00054 (0 hom.)
• Consequence: ZSWIM6 NM_020928.2 inframe_insertion
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.671

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant 5-61332326-G-GGGCGGC is Benign according to our data. Variant chr5-61332326-G-GGGCGGC is described in ClinVar as [Likely_benign]. Clinvar id is 1640326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 113 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZSWIM6	NM_020928.2	c.69_74dup	p.Gly25_Gly26dup	inframe_insertion	1/14	ENST00000252744.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZSWIM6	ENST00000252744.6	c.69_74dup	p.Gly25_Gly26dup	inframe_insertion	1/14	5	NM_020928.2	P1

Frequencies

GnomAD3 genomes AF: 0.000763 AC: 113 AN: 148044 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000404

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000465

Gnomad OTH AF: 0.000984

GnomAD4 exome AF: 0.000538 AC: 522 AN: 969388 Hom.: 0 Cov.: 11 AF XY: 0.000544 AC XY: 249 AN XY: 457596

Gnomad4 AFR exome AF: 0.00122

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000514

Gnomad4 SAS exome AF: 0.000486

Gnomad4 FIN exome AF: 0.0000724

Gnomad4 NFE exome AF: 0.000549

Gnomad4 OTH exome AF: 0.000580

GnomAD4 genome AF: 0.000763 AC: 113 AN: 148140 Hom.: 0 Cov.: 26 AF XY: 0.000775 AC XY: 56 AN XY: 72244

Gnomad4 AFR AF: 0.00175

Gnomad4 AMR AF: 0.000404

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000417

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000465

Gnomad4 OTH AF: 0.000974

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Dec 21, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	ZSWIM6: BS1 -

ZSWIM6-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 29, 2022

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs565100893; hg19: chr5-60628153;