rs1243690822

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_020928.2(ZSWIM6):c.75_95delGGGCAGCAGCGGCGGCGGCGG(p.Gly26_Gly32del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,055,464 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 DEL_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 (★★). Synonymous variant affecting the same amino acid position (i.e. G25G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

ZSWIM6
NM_020928.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.10

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: Benign. The variant received -12 ACMG points.

BP6

Variant 5-61332333-GGCGGCGGCGGCGGGGGCAGCA-G is Benign according to our data. Variant chr5-61332333-GGCGGCGGCGGCGGGGGCAGCA-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1474417.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 59 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM6	NM_020928.2 link	c.75_95delGGGCAGCAGCGGCGGCGGCGG	p.Gly26_Gly32del	disruptive_inframe_deletion	Exon 1 of 14	ENST00000252744.6	NP_065979.1	Q9HCJ5
ENSG00000288936		n.61332354_61332334delTGCTGCCCCCGCCGCCGCCGC		bidirectional_gene_fusion
LOC105378994	XR_007058781.1 link	n.-138_-118delTGCTGCCCCCGCCGCCGCCGC		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSWIM6	ENST00000252744.6 link	c.75_95delGGGCAGCAGCGGCGGCGGCGG	p.Gly26_Gly32del	disruptive_inframe_deletion	Exon 1 of 14	5	NM_020928.2	ENSP00000252744.5		Q9HCJ5

Frequencies

GnomAD3 genomes

AF:

0.000446

AC:

AN:

132364

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00119

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000465

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000766

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000511

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

442

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:

0.0000563

AC:

AN:

923030

Hom.:

AF XY:

0.0000666

AC XY:

AN XY:

435746

show subpopulations

African (AFR)

AF:

0.00109

AC:

AN:

19328

American (AMR)

AF:

0.000637

AC:

AN:

4706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9906

East Asian (EAS)

AF:

0.000391

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:

0.000393

AC:

AN:

2546

European-Non Finnish (NFE)

AF:

0.00000872

AC:

AN:

803178

Other (OTH)

AF:

0.000376

AC:

AN:

34616

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

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:

0.000446

AC:

AN:

132434

Hom.:

Cov.:

AF XY:

0.000530

AC XY:

AN XY:

64188

show subpopulations

African (AFR)

AF:

0.00119

AC:

AN:

39516

American (AMR)

AF:

0.000464

AC:

AN:

12920

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3228

East Asian (EAS)

AF:

0.000769

AC:

AN:

3902

South Asian (SAS)

AF:

0.00

AC:

AN:

3198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8090

Middle Eastern (MID)

AF:

0.00

AC:

AN:

258

European-Non Finnish (NFE)

AF:

0.0000511

AC:

AN:

58686

Other (OTH)

AF:

0.00

AC:

AN:

1850

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

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:

0.0000843

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Apr 25, 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. -

not provided

Benign:1

Oct 28, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.1

Mutation Taster

=187/13

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