5-61332326-GGGCGGCGGCGGC-GGGCGGCGGCGGCGGCGGC

Variant names:

• chr5-61332326-G-GGGCGGC
• rs565100893
• NM_020928.2:c.69_74dupCGGCGG

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_020928.2(ZSWIM6):​c.69_74dupCGGCGG​(p.Gly24_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 0.000568 in 1,117,528 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G25G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00076 (0 hom., cov: 26)
  • Exomes 𝑓: 0.00054 (0 hom.)
• Consequence: ZSWIM6 NM_020928.2 disruptive_inframe_insertion
• Clinical Significance: Likely 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 -12 ACMG points.

• BP6: Variant 5-61332326-G-GGGCGGC is Benign according to our data. Variant chr5-61332326-G-GGGCGGC is described in ClinVar as Likely_benign. ClinVar VariationId is 1640326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 113 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM6	NM_020928.2	MANE Select	c.69_74dupCGGCGG	p.Gly24_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.69_74dupCGGCGG	p.Gly24_Gly25dup	disruptive_inframe_insertion	Exon 1 of 14	ENSP00000252744.5	Q9HCJ5
	ENSG00000288936	ENST00000821437.1		n.17_22dupGCCGCC		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000288936	ENST00000821446.1		n.7_12dupGCCGCC		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.000763 AC: 113 AN: 148044 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000404

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000465

Gnomad OTH AF: 0.000984

GnomAD2 exomes AF: 0.00 AC: 0 AN: 456 AF XY: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000538 AC: 522 AN: 969388 Hom.: 0 Cov.: 11 AF XY: 0.000544 AC XY: 249 AN XY: 457596

African (AFR) AF: 0.00122 AC: 24 AN: 19710

American (AMR) AF: 0.00 AC: 0 AN: 5016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10110

East Asian (EAS) AF: 0.0000514 AC: 1 AN: 19448

South Asian (SAS) AF: 0.000486 AC: 9 AN: 18528

European-Finnish (FIN) AF: 0.0000724 AC: 1 AN: 13812

Middle Eastern (MID) AF: 0.00112 AC: 3 AN: 2670

European-Non Finnish (NFE) AF: 0.000549 AC: 463 AN: 843904

Other (OTH) AF: 0.000580 AC: 21 AN: 36190

GnomAD4 genome AF: 0.000763 AC: 113 AN: 148140 Hom.: 0 Cov.: 26 AF XY: 0.000775 AC XY: 56 AN XY: 72244

African (AFR) AF: 0.00175 AC: 72 AN: 41054

American (AMR) AF: 0.000404 AC: 6 AN: 14866

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3412

East Asian (EAS) AF: 0.00 AC: 0 AN: 5072

South Asian (SAS) AF: 0.000417 AC: 2 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.000465 AC: 31 AN: 66644

Other (OTH) AF: 0.000974 AC: 2 AN: 2054

Alfa AF: 0.00 Hom.: 61

ClinVar

ClinVar submissions

Significance: 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		0.67
Mutation Taster		=77/23	polymorphism

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;