5-61332326-GGGCGGCGGCGGC-GGGCGGCGGCGGCGGC

Variant names:

• chr5-61332326-G-GGGC
• rs565100893
• NM_020928.2:c.72_74dupCGG

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.72_74dupCGG​(p.Gly25dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,116,596 control chromosomes in the GnomAD database, including 11,212 homozygotes. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G25G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.14 (1478 hom., cov: 26)
  • Exomes 𝑓: 0.16 (9734 hom.)
• Consequence: ZSWIM6 NM_020928.2 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.671
• Publications: 2 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• 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 5-61332326-G-GGGC is Benign according to our data. Variant chr5-61332326-G-GGGC is described in ClinVar as Benign. ClinVar VariationId is 1257965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.161 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM6	NM_020928.2	MANE Select	c.72_74dupCGG	p.Gly25dup	disruptive_inframe_insertion	Exon 1 of 14	NP_065979.1	Q9HCJ5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM6	ENST00000252744.6	TSL:5 MANE Select	c.72_74dupCGG	p.Gly25dup	disruptive_inframe_insertion	Exon 1 of 14	ENSP00000252744.5	Q9HCJ5
	ENSG00000288936	ENST00000821437.1		n.20_22dupGCC		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000288936	ENST00000821446.1		n.10_12dupGCC		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20172 AN: 147992 Hom.: 1476 Cov.: 26

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.00452

Gnomad SAS AF: 0.0827

Gnomad FIN AF: 0.0959

Gnomad MID AF: 0.154

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.161

GnomAD2 exomes AF: 0.0943 AC: 43 AN: 456 AF XY: 0.0822

Gnomad ASJ exome AF: 0.00

Gnomad FIN exome AF: 0.0183

Gnomad NFE exome AF: 0.165

Gnomad OTH exome AF: 0.250

GnomAD4 exome AF: 0.155 AC: 150298 AN: 968508 Hom.: 9734 Cov.: 11 AF XY: 0.154 AC XY: 70200 AN XY: 457136

African (AFR) AF: 0.0962 AC: 1894 AN: 19698

American (AMR) AF: 0.0721 AC: 360 AN: 4994

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 1328 AN: 10102

East Asian (EAS) AF: 0.00298 AC: 58 AN: 19446

South Asian (SAS) AF: 0.0769 AC: 1423 AN: 18516

European-Finnish (FIN) AF: 0.0540 AC: 743 AN: 13758

Middle Eastern (MID) AF: 0.142 AC: 378 AN: 2664

European-Non Finnish (NFE) AF: 0.165 AC: 138900 AN: 843180

Other (OTH) AF: 0.144 AC: 5214 AN: 36150

GnomAD4 genome AF: 0.136 AC: 20173 AN: 148088 Hom.: 1478 Cov.: 26 AF XY: 0.131 AC XY: 9458 AN XY: 72220

African (AFR) AF: 0.118 AC: 4843 AN: 41044

American (AMR) AF: 0.132 AC: 1958 AN: 14860

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 605 AN: 3412

East Asian (EAS) AF: 0.00453 AC: 23 AN: 5072

South Asian (SAS) AF: 0.0822 AC: 394 AN: 4796

European-Finnish (FIN) AF: 0.0959 AC: 867 AN: 9036

Middle Eastern (MID) AF: 0.149 AC: 43 AN: 288

European-Non Finnish (NFE) AF: 0.164 AC: 10910 AN: 66618

Other (OTH) AF: 0.160 AC: 328 AN: 2054

Alfa AF: 0.0447 Hom.: 61

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	ZSWIM6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.67
Mutation Taster		=77/23	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs565100893; hg19: chr5-60628153; COSMIC: COSV53172566;