5-61332354-AGCGGCGGCG-AGCGGCGGCGGCG

Variant names:

• chr5-61332354-A-AGCG
• rs528020839
• NM_020928.2:c.98_100dupGCG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_020928.2(ZSWIM6):​c.98_100dupGCG​(p.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 0.119 in 1,004,548 control chromosomes in the GnomAD database, including 7,053 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1078 hom., cov: 29)
  • Exomes 𝑓: 0.12 (5975 hom.)
• Consequence: ZSWIM6 NM_020928.2 disruptive_inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• 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: Benign. The variant received -16 ACMG points.

• BP6: Variant 5-61332354-A-AGCG is Benign according to our data. Variant chr5-61332354-A-AGCG is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 437395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

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.98_100dupGCG	p.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.98_100dupGCG	p.Gly33dup	disruptive_inframe_insertion	Exon 1 of 14	ENSP00000252744.5
	ENSG00000288936	ENST00000821437.1		n.-9_-7dupCGC		upstream_gene	N/A
	ENSG00000288936	ENST00000821446.1		n.-19_-17dupCGC		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.109 AC: 15129 AN: 138814 Hom.: 1077 Cov.: 29

Gnomad AFR AF: 0.0281

Gnomad AMI AF: 0.0778

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.0819

Gnomad EAS AF: 0.00210

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0714

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.102

GnomAD2 exomes AF: 0.0695 AC: 21 AN: 302 AF XY: 0.0795

Gnomad AMR exome AF: 0.00

Gnomad FIN exome AF: 0.0500

Gnomad NFE exome AF: 0.0742

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.121 AC: 104517 AN: 865634 Hom.: 5975 Cov.: 28 AF XY: 0.120 AC XY: 48763 AN XY: 405888

African (AFR) AF: 0.0123 AC: 215 AN: 17458

American (AMR) AF: 0.0871 AC: 247 AN: 2836

Ashkenazi Jewish (ASJ) AF: 0.0619 AC: 451 AN: 7288

East Asian (EAS) AF: 0.00140 AC: 16 AN: 11462

South Asian (SAS) AF: 0.127 AC: 2264 AN: 17772

European-Finnish (FIN) AF: 0.0296 AC: 202 AN: 6822

Middle Eastern (MID) AF: 0.0651 AC: 133 AN: 2042

European-Non Finnish (NFE) AF: 0.127 AC: 98075 AN: 769334

Other (OTH) AF: 0.0952 AC: 2914 AN: 30620

GnomAD4 genome AF: 0.109 AC: 15138 AN: 138914 Hom.: 1078 Cov.: 29 AF XY: 0.113 AC XY: 7626 AN XY: 67772

African (AFR) AF: 0.0280 AC: 1082 AN: 38648

American (AMR) AF: 0.198 AC: 2792 AN: 14120

Ashkenazi Jewish (ASJ) AF: 0.0819 AC: 267 AN: 3262

East Asian (EAS) AF: 0.00211 AC: 10 AN: 4740

South Asian (SAS) AF: 0.132 AC: 602 AN: 4566

European-Finnish (FIN) AF: 0.176 AC: 1450 AN: 8260

Middle Eastern (MID) AF: 0.0736 AC: 19 AN: 258

European-Non Finnish (NFE) AF: 0.139 AC: 8657 AN: 62300

Other (OTH) AF: 0.101 AC: 193 AN: 1912

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

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

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; COSMIC: COSV53174378;