Genetic Variant ZSWIM6:p.Ala147_Gly151dup (chr5-61332698-T-TGGCGGCGGCGGCGCG) – 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.440_454dupCGGGCGGCGGCGGCG(p.Ala147_Gly151dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000424 in 967,230 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000024 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

ZSWIM6
NM_020928.2 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.07

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:

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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 38 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM6	NM_020928.2 link	c.440_454dupCGGGCGGCGGCGGCG	p.Ala147_Gly151dup	disruptive_inframe_insertion	Exon 1 of 14	ENST00000252744.6	NP_065979.1	Q9HCJ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSWIM6	ENST00000252744.6 link	c.440_454dupCGGGCGGCGGCGGCG	p.Ala147_Gly151dup	disruptive_inframe_insertion	Exon 1 of 14	5	NM_020928.2	ENSP00000252744.5		Q9HCJ5

Frequencies

GnomAD3 genomes

AF:

0.0000242

AC:

AN:

123872

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:

0.0000521

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000451

AC:

AN:

843358

Hom.:

Cov.:

AF XY:

0.0000306

AC XY:

AN XY:

392336

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15762

American (AMR)

AF:

0.00

AC:

AN:

1450

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5782

East Asian (EAS)

AF:

0.00

AC:

AN:

4088

South Asian (SAS)

AF:

0.00

AC:

AN:

19536

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1704

European-Non Finnish (NFE)

AF:

0.0000499

AC:

AN:

761836

Other (OTH)

AF:

0.00

AC:

AN:

27586

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000242

AC:

AN:

123872

Hom.:

Cov.:

AF XY:

0.0000332

AC XY:

AN XY:

60160

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

34006

American (AMR)

AF:

0.00

AC:

AN:

13026

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3066

East Asian (EAS)

AF:

0.00

AC:

AN:

3680

South Asian (SAS)

AF:

0.00

AC:

AN:

3700

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6192

Middle Eastern (MID)

AF:

0.00

AC:

AN:

182

European-Non Finnish (NFE)

AF:

0.0000521

AC:

AN:

57570

Other (OTH)

AF:

0.00

AC:

AN:

1716

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.608

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 v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.1

Mutation Taster

=77/23

polymorphism

(source)

Splicing

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

Publications

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5-61332698-TGGCGGCGGCGGCGCG-TGGCGGCGGCGGCGCGGGCGGCGGCGGCGCG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over