Genetic Variant ZSWIM6:p.Gly33del (chr5-61332354-AGCG-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The ENST00000252744.6(ZSWIM6):c.98_100delGCG(p.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 0.0000767 in 1,003,512 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000087 ( 0 hom. )

Consequence

ZSWIM6
ENST00000252744.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP3

Nonframeshift variant in repetitive region in ENST00000252744.6

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000252744.6. 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.98_100delGCG	p.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.98_100delGCG	p.Gly33del	disruptive_inframe_deletion	Exon 1 of 14	ENSP00000252744.5
ENSG00000288936	ENST00000821437.1		n.-9_-7delCGC		upstream_gene	N/A
ENSG00000288936	ENST00000821446.1		n.-19_-17delCGC		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000144

AC:

AN:

138856

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000709

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:

0.0000160

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

302

AF XY:

0.00

Gnomad AMR 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:

0.0000867

AC:

AN:

864656

Hom.:

AF XY:

0.000116

AC XY:

AN XY:

405430

show subpopulations

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

African (AFR)

AF:

0.000172

AC:

AN:

17438

American (AMR)

AF:

0.00

AC:

AN:

2842

Ashkenazi Jewish (ASJ)

AF:

0.000137

AC:

AN:

7278

East Asian (EAS)

AF:

0.000874

AC:

AN:

11436

South Asian (SAS)

AF:

0.000225

AC:

AN:

17744

European-Finnish (FIN)

AF:

0.000439

AC:

AN:

6830

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2040

European-Non Finnish (NFE)

AF:

0.0000638

AC:

AN:

768464

Other (OTH)

AF:

0.000163

AC:

AN:

30584

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.288

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:

0.0000144

AC:

AN:

138856

Hom.:

Cov.:

AF XY:

0.0000148

AC XY:

AN XY:

67684

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38546

American (AMR)

AF:

0.0000709

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:

8266

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.0000160

AC:

AN:

62322

Other (OTH)

AF:

0.00

AC:

AN:

1888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

Mutation Taster

=81/19

polymorphism

(source)

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

Publications

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5-61332354-AGCGGCGGCG-AGCGGCG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over