chr5-61332283-G-C

Variant names:

• chr5-61332283-G-C
• rs1744263423
• NM_020928.2:c.11G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020928.2(ZSWIM6):​c.11G>C​(p.Arg4Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000394 in 1,014,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R4H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000039 (0 hom.)
• Consequence: ZSWIM6 NM_020928.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.88
• Publications: 0 publications found

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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000288936 (HGNC:59059):

LOC105378994 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38003093).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020928.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM6	NM_020928.2	MANE Select	c.11G>C	p.Arg4Pro	missense	Exon 1 of 14	NP_065979.1	Q9HCJ5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM6	ENST00000252744.6	TSL:5 MANE Select	c.11G>C	p.Arg4Pro	missense	Exon 1 of 14	ENSP00000252744.5	Q9HCJ5
	ENSG00000288936	ENST00000821437.1		n.66C>G		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000288936	ENST00000821446.1		n.56C>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000394 AC: 4 AN: 1014318 Hom.: 0 Cov.: 28 AF XY: 0.00000418 AC XY: 2 AN XY: 478226

African (AFR) AF: 0.00 AC: 0 AN: 20632

American (AMR) AF: 0.00 AC: 0 AN: 6012

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11568

East Asian (EAS) AF: 0.00 AC: 0 AN: 21368

South Asian (SAS) AF: 0.00 AC: 0 AN: 19008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16824

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3700

European-Non Finnish (NFE) AF: 0.00000456 AC: 4 AN: 876296

Other (OTH) AF: 0.00 AC: 0 AN: 38910

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
PhyloP100		6.9
PromoterAI		-0.013	Neutral
Varity_R		0.38
gMVP		0.62
Mutation Taster		=40/60	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1744263423; hg19: chr5-60628110;