chr5-61332326-GGGCGGC-G

Variant names:

• chr5-61332326-GGGCGGC-G
• rs565100893
• NM_020928.2:c.69_74delCGGCGG

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.69_74delCGGCGG​(p.Gly24_Gly25del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.044 in 1,117,382 control chromosomes in the GnomAD database, including 1,570 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (222 hom., cov: 26)
  • Exomes 𝑓: 0.044 (1348 hom.)
• Consequence: ZSWIM6 NM_020928.2 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.15
• 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-GGGCGGC-G is Benign according to our data. Variant chr5-61332326-GGGCGGC-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 218778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.173 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.69_74delCGGCGG	p.Gly24_Gly25del	disruptive_inframe_deletion	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.69_74delCGGCGG	p.Gly24_Gly25del	disruptive_inframe_deletion	Exon 1 of 14	ENSP00000252744.5	Q9HCJ5
	ENSG00000288936	ENST00000821437.1		n.17_22delGCCGCC		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000288936	ENST00000821446.1		n.7_12delGCCGCC		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0410 AC: 6068 AN: 148034 Hom.: 217 Cov.: 26

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.0573

Gnomad AMR AF: 0.0498

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.0417

Gnomad MID AF: 0.0449

Gnomad NFE AF: 0.0407

Gnomad OTH AF: 0.0330

GnomAD2 exomes AF: 0.0175 AC: 8 AN: 456 AF XY: 0.0240

Gnomad ASJ exome AF: 0.00

Gnomad FIN exome AF: 0.0183

Gnomad NFE exome AF: 0.0174

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0445 AC: 43117 AN: 969252 Hom.: 1348 AF XY: 0.0449 AC XY: 20548 AN XY: 457506

African (AFR) AF: 0.0110 AC: 217 AN: 19710

American (AMR) AF: 0.0553 AC: 277 AN: 5012

Ashkenazi Jewish (ASJ) AF: 0.0206 AC: 208 AN: 10108

East Asian (EAS) AF: 0.0900 AC: 1750 AN: 19436

South Asian (SAS) AF: 0.178 AC: 3301 AN: 18526

European-Finnish (FIN) AF: 0.0365 AC: 503 AN: 13798

Middle Eastern (MID) AF: 0.0461 AC: 123 AN: 2670

European-Non Finnish (NFE) AF: 0.0411 AC: 34639 AN: 843808

Other (OTH) AF: 0.0580 AC: 2099 AN: 36184

GnomAD4 genome AF: 0.0411 AC: 6091 AN: 148130 Hom.: 222 Cov.: 26 AF XY: 0.0448 AC XY: 3235 AN XY: 72240

African (AFR) AF: 0.0130 AC: 533 AN: 41052

American (AMR) AF: 0.0498 AC: 740 AN: 14864

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 68 AN: 3412

East Asian (EAS) AF: 0.125 AC: 633 AN: 5068

South Asian (SAS) AF: 0.183 AC: 880 AN: 4796

European-Finnish (FIN) AF: 0.0417 AC: 377 AN: 9044

Middle Eastern (MID) AF: 0.0486 AC: 14 AN: 288

European-Non Finnish (NFE) AF: 0.0407 AC: 2712 AN: 66644

Other (OTH) AF: 0.0399 AC: 82 AN: 2054

Alfa AF: 0.00955 Hom.: 61

ClinVar

ClinVar submissions

Significance: Benign/Likely 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		3.1
Mutation Taster		=192/8	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: COSV53179213;