5-61332354-AGCGGCGGCG-AGCGGCGGCGGCGGCG

Variant names:

• chr5-61332354-A-AGCGGCG
• rs528020839
• NM_020928.2:c.95_100dupGCGGCG

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6 BS2

The NM_020928.2(ZSWIM6):​c.95_100dupGCGGCG​(p.Gly32_Gly33dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,004,978 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: ZSWIM6 NM_020928.2 disruptive_inframe_insertion
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.00
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• acromelic frontonasal dysostosis

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000288936 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP6: Variant 5-61332354-A-AGCGGCG is Benign according to our data. Variant chr5-61332354-A-AGCGGCG is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 1637073.
• BS2: High AC in GnomAd4 at 18 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020928.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM6	NM_020928.2	MANE Select	c.95_100dupGCGGCG	p.Gly32_Gly33dup	disruptive_inframe_insertion	Exon 1 of 14	NP_065979.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM6	ENST00000252744.6	TSL:5 MANE Select	c.95_100dupGCGGCG	p.Gly32_Gly33dup	disruptive_inframe_insertion	Exon 1 of 14	ENSP00000252744.5
	ENSG00000288936	ENST00000821437.1		n.-12_-7dupCGCCGC		upstream_gene	N/A
	ENSG00000288936	ENST00000821446.1		n.-22_-17dupCGCCGC		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.000130 AC: 18 AN: 138862 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000425

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: 0.000193

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000222 AC: 192 AN: 866116 Hom.: 0 Cov.: 28 AF XY: 0.000219 AC XY: 89 AN XY: 406152

African (AFR) AF: 0.00 AC: 0 AN: 17458

American (AMR) AF: 0.00105 AC: 3 AN: 2844

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7290

East Asian (EAS) AF: 0.00 AC: 0 AN: 11462

South Asian (SAS) AF: 0.000113 AC: 2 AN: 17774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6838

Middle Eastern (MID) AF: 0.000490 AC: 1 AN: 2042

European-Non Finnish (NFE) AF: 0.000227 AC: 175 AN: 769766

Other (OTH) AF: 0.000359 AC: 11 AN: 30642

GnomAD4 genome AF: 0.000130 AC: 18 AN: 138862 Hom.: 0 Cov.: 29 AF XY: 0.0000739 AC XY: 5 AN XY: 67684

African (AFR) AF: 0.00 AC: 0 AN: 38548

American (AMR) AF: 0.000425 AC: 6 AN: 14110

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3264

East Asian (EAS) AF: 0.00 AC: 0 AN: 4756

South Asian (SAS) AF: 0.00 AC: 0 AN: 4576

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.000193 AC: 12 AN: 62324

Other (OTH) AF: 0.00 AC: 0 AN: 1888

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000253

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	1	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=72/28	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs528020839; hg19: chr5-60628181;