5-61332333-GGCGGCGGCGGCGGGGGCAGCA-GGCGGCGGCGGCGGGGGCAGCAGCGGCGGCGGCGGGGGCAGCA

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_020928.2(ZSWIM6):c.75_95dupGGGCAGCAGCGGCGGCGGCGG(p.Gly32_Gly33insGlySerSerGlyGlyGlyGly) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000755 in 132,364 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000076 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000054 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZSWIM6
NM_020928.2 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.605

Publications

0 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 -2 ACMG points.

BP6

Variant 5-61332333-G-GGCGGCGGCGGCGGGGGCAGCA is Benign according to our data. Variant chr5-61332333-G-GGCGGCGGCGGCGGGGGCAGCA is described in ClinVar as Likely_benign. ClinVar VariationId is 2473111.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM6	NM_020928.2 link	c.75_95dupGGGCAGCAGCGGCGGCGGCGG	p.Gly32_Gly33insGlySerSerGlyGlyGlyGly	disruptive_inframe_insertion	Exon 1 of 14	ENST00000252744.6	NP_065979.1	Q9HCJ5
LOC105378994	XR_007058781.1 link	n.-138_-118dupTGCTGCCCCCGCCGCCGCCGC		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZSWIM6	ENST00000252744.6 link	c.75_95dupGGGCAGCAGCGGCGGCGGCGG	p.Gly32_Gly33insGlySerSerGlyGlyGlyGly	disruptive_inframe_insertion	Exon 1 of 14	5	NM_020928.2	ENSP00000252744.5	Q9HCJ5
ENSG00000288936	ENST00000821437.1 link	n.-6_15dupTGCTGCCCCCGCCGCCGCCGC		non_coding_transcript_exon_variant	Exon 1 of 2
ENSG00000288936	ENST00000821446.1 link	n.-16_5dupTGCTGCCCCCGCCGCCGCCGC		non_coding_transcript_exon_variant	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.00000755

AC:

AN:

132364

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000170

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000542

AC:

AN:

923030

Hom.:

Cov.:

AF XY:

0.00000229

AC XY:

AN XY:

435746

show subpopulations

African (AFR)

AF:

0.0000517

AC:

AN:

19328

American (AMR)

AF:

0.00

AC:

AN:

4706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9906

East Asian (EAS)

AF:

0.00

AC:

AN:

17900

South Asian (SAS)

AF:

0.00

AC:

AN:

17820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

13030

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2546

European-Non Finnish (NFE)

AF:

0.00000374

AC:

AN:

803178

Other (OTH)

AF:

0.0000289

AC:

AN:

34616

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.00000755

AC:

AN:

132364

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

64110

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39420

American (AMR)

AF:

0.00

AC:

AN:

12904

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3228

East Asian (EAS)

AF:

0.00

AC:

AN:

3916

South Asian (SAS)

AF:

0.00

AC:

AN:

3196

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8090

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.0000170

AC:

AN:

58692

Other (OTH)

AF:

0.00

AC:

AN:

1850

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Jan 27, 2023

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.60

Mutation Taster

=79/21

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over