Variant 5-61332333-GGCGGCGGCGGCGGGGGCAGCA-GGCGGCGGCGGCGGGGGCAGCAGCGGCGGCGGCGGGGGCAGCA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_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. 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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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 id 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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	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

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

Gnomad4 AFR exome

AF:

0.0000517

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000374

Gnomad4 OTH exome

AF:

0.0000289

GnomAD4 genome

AF:

0.00000755

AC:

AN:

132364

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

64110

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000170

Gnomad4 OTH

AF:

0.00

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

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over