5-61332326-GGGC-G

Variant summary

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

The NM_020928.2(ZSWIM6):c.72_74del(p.Gly26del) variant causes a 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 inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.17

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-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 GnomAd at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZSWIM6	NM_020928.2	c.72_74del	p.Gly26del	inframe_deletion	1/14	ENST00000252744.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZSWIM6	ENST00000252744.6	c.72_74del	p.Gly26del	inframe_deletion	1/14	5	NM_020928.2	P1

Frequencies

GnomAD3 genomes AF: 0.0000946 AC: 14 AN: 148036 Hom.: 0 Cov.: 26

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: 3 AN: 456 Hom.: 0 AF XY: 0.00685 AC XY: 2 AN XY: 292

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.: 1 AF XY: 0.00130 AC XY: 587 AN XY: 451164

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: 14 AN: 148132 Hom.: 0 Cov.: 26 AF XY: 0.0000969 AC XY: 7 AN XY: 72240

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

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Apr 14, 2023

- -

ZSWIM6-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 22, 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

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: rs565100893; hg19: chr5-60628153;