Genetic Variant ZSWIM6:p.Gly32_Gly33del (chr5-61332354-AGCGGCG-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_020928.2(ZSWIM6):c.95_100delGCGGCG(p.Gly32_Gly33del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000607 in 1,004,970 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000029 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

ZSWIM6
NM_020928.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.622

Publications

3 publications found

Variant links:

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)

ZSWIM6 links:

ENSG00000288936 (HGNC:):

ENSG00000288936 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 57 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM6	NM_020928.2	MANE Select	c.95_100delGCGGCG	p.Gly32_Gly33del	disruptive_inframe_deletion	Exon 1 of 14	NP_065979.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ZSWIM6	ENST00000252744.6	TSL:5 MANE Select	c.95_100delGCGGCG	p.Gly32_Gly33del	disruptive_inframe_deletion	Exon 1 of 14	ENSP00000252744.5
ENSG00000288936	ENST00000821437.1		n.-12_-7delCGCCGC		upstream_gene	N/A
ENSG00000288936	ENST00000821446.1		n.-22_-17delCGCCGC		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000288

AC:

AN:

138862

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000519

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000321

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000658

AC:

AN:

866108

Hom.:

AF XY:

0.0000739

AC XY:

AN XY:

406144

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17458

American (AMR)

AF:

0.00

AC:

AN:

2844

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7290

East Asian (EAS)

AF:

0.00

AC:

AN:

11462

South Asian (SAS)

AF:

0.00

AC:

AN:

17772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6838

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2042

European-Non Finnish (NFE)

AF:

0.0000727

AC:

AN:

769760

Other (OTH)

AF:

0.0000326

AC:

AN:

30642

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000288

AC:

AN:

138862

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

67684

show subpopulations

African (AFR)

AF:

0.0000519

AC:

AN:

38548

American (AMR)

AF:

0.00

AC:

AN:

14110

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3264

East Asian (EAS)

AF:

0.00

AC:

AN:

4756

South Asian (SAS)

AF:

0.00

AC:

AN:

4576

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8268

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.0000321

AC:

AN:

62324

Other (OTH)

AF:

0.00

AC:

AN:

1888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000491

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.62

Mutation Taster

=181/19

polymorphism

(source)

Splicing

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

Publications

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5-61332354-AGCGGCGGCG-AGCG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over