rs1219369551

Variant names:

• chr5-61332298-C-T
• rs1219369551
• NM_020928.2:c.26C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020928.2(ZSWIM6):​c.26C>T​(p.Pro9Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 151,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 9.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZSWIM6 NM_020928.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.09
• 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:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16832492).

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.26C>T	p.Pro9Leu	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.26C>T	p.Pro9Leu	missense	Exon 1 of 14	ENSP00000252744.5	Q9HCJ5
	ENSG00000288936	ENST00000821437.1		n.51G>A		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000288936	ENST00000821446.1		n.41G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.00000662 AC: 1 AN: 151052 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.81e-7 AC: 1 AN: 1019056 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 482296

African (AFR) AF: 0.00 AC: 0 AN: 20696

American (AMR) AF: 0.00 AC: 0 AN: 6052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11588

East Asian (EAS) AF: 0.00 AC: 0 AN: 21474

South Asian (SAS) AF: 0.00 AC: 0 AN: 19106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16648

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3628

European-Non Finnish (NFE) AF: 0.00000114 AC: 1 AN: 880798

Other (OTH) AF: 0.00 AC: 0 AN: 39066

GnomAD4 genome AF: 0.00000662 AC: 1 AN: 151052 Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1 AN XY: 73748

African (AFR) AF: 0.0000242 AC: 1 AN: 41352

American (AMR) AF: 0.00 AC: 0 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10068

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67706

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.00027	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.56	T
M_CAP	Pathogenic	0.63	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.1
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.12
Sift	Benign	0.16	T
Sift4G	Uncertain	0.024	D
Polyphen		0.041	B
Vest4		0.27
MutPred		0.27		Loss of glycosylation at P9 (P = 0.005)
MVP		0.076
MPC		0.51
ClinPred		0.32	T
GERP RS		2.8
PromoterAI		-0.12	Neutral
Varity_R		0.12
gMVP		0.56
Mutation Taster		=66/34	polymorphism

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

Other links and lift over

dbSNP: rs1219369551; hg19: chr5-60628125;