5-61332326-GGGC-G

Variant names:

• chr5-61332326-GGGC-G
• rs565100893
• NM_020928.2:c.72_74delCGG

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.72_74delCGG​(p.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 0.000967 in 1,103,948 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000095 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0011 (1 hom.)
• Consequence: ZSWIM6 NM_020928.2 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.17
• 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-GGGC-G is Benign according to our data. Variant chr5-61332326-GGGC-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1636008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 14 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.72_74delCGG	p.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.72_74delCGG	p.Gly25del	disruptive_inframe_deletion	Exon 1 of 14	ENSP00000252744.5	Q9HCJ5
	ENSG00000288936	ENST00000821437.1		n.20_22delGCC		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000288936	ENST00000821446.1		n.10_12delGCC		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0000946 AC: 14 AN: 148036 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.000122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000673

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000900

Gnomad OTH AF: 0.000493

GnomAD2 exomes AF: 0.00658 AC: 3 AN: 456 AF XY: 0.00685

Gnomad ASJ exome AF: 0.00

Gnomad FIN exome AF: 0.0138

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00110 AC: 1053 AN: 955816 Hom.: 1 AF XY: 0.00130 AC XY: 587 AN XY: 451164

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00128 AC: 25 AN: 19556

American (AMR) AF: 0.00447 AC: 22 AN: 4926

Ashkenazi Jewish (ASJ) AF: 0.00290 AC: 29 AN: 10004

East Asian (EAS) AF: 0.00593 AC: 114 AN: 19230

South Asian (SAS) AF: 0.000548 AC: 10 AN: 18256

European-Finnish (FIN) AF: 0.00606 AC: 82 AN: 13536

Middle Eastern (MID) AF: 0.00189 AC: 5 AN: 2650

European-Non Finnish (NFE) AF: 0.000843 AC: 701 AN: 831902

Other (OTH) AF: 0.00182 AC: 65 AN: 35756

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000945 AC: 14 AN: 148132 Hom.: 0 Cov.: 26 AF XY: 0.0000969 AC XY: 7 AN XY: 72240

African (AFR) AF: 0.000122 AC: 5 AN: 41054

American (AMR) AF: 0.0000673 AC: 1 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: 0.000208 AC: 1 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: 0.0000900 AC: 6 AN: 66638

Other (OTH) AF: 0.000487 AC: 1 AN: 2052

Alfa AF: 0.00 Hom.: 61

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs565100893; hg19: chr5-60628153;