rs772099709

chr5-61332698-TGGCGGCGGCGGCGCG-Tchr5-61332698-TGGCGGCGGCGGCGCG-TGGCGGCGGCGGCGCGGGCGGCGGCGGCGCG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_020928.2(ZSWIM6):c.440_454del(p.Ala147_Gly151del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 967,264 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 27)
  • Exomes 𝑓: 0.000097 (1 hom.)
• Consequence: ZSWIM6 NM_020928.2 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.17

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd at 28 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZSWIM6	NM_020928.2	c.440_454del	p.Ala147_Gly151del	inframe_deletion	1/14	ENST00000252744.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZSWIM6	ENST00000252744.6	c.440_454del	p.Ala147_Gly151del	inframe_deletion	1/14	5	NM_020928.2	P1

Frequencies

GnomAD3 genomes AF: 0.000226 AC: 28 AN: 123872 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.000559

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000768

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: 0.000139

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000972 AC: 82 AN: 843358 Hom.: 1 AF XY: 0.0000816 AC XY: 32 AN XY: 392336

Gnomad4 AFR exome AF: 0.000317

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000489

Gnomad4 SAS exome AF: 0.000154

Gnomad4 FIN exome AF: 0.000178

Gnomad4 NFE exome AF: 0.0000893

Gnomad4 OTH exome AF: 0.0000363

GnomAD4 genome AF: 0.000226 AC: 28 AN: 123906 Hom.: 0 Cov.: 27 AF XY: 0.000166 AC XY: 10 AN XY: 60188

Gnomad4 AFR AF: 0.000558

Gnomad4 AMR AF: 0.0000767

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000139

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Acromelic frontonasal dysostosis Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Mar 05, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs772099709; hg19: chr5-60628525;