rs1744263423

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-61332283-G-A
• chr5-61332283-G-C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_020928.2(ZSWIM6):​c.11G>A​(p.Arg4His) variant causes a missense change. The variant allele was found at a frequency of 0.00000986 in 1,014,318 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000099 (0 hom.)
• Consequence: ZSWIM6 NM_020928.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3147957).
• BS2: High AC in GnomAdExome4 at 10 AD gene.

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>A	p.Arg4His	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>A	p.Arg4His	missense	Exon 1 of 14	ENSP00000252744.5	Q9HCJ5
	ENSG00000288936	ENST00000821437.1		n.66C>T		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000288936	ENST00000821446.1		n.56C>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000986 AC: 10 AN: 1014318 Hom.: 0 Cov.: 28 AF XY: 0.0000125 AC XY: 6 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: 0.0000114 AC: 10 AN: 876296

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

GnomAD4 genome Cov.: 32

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	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.00081	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.036
FATHMM_MKL	Benign	0.0089	N
LIST_S2	Uncertain	0.87	D
M_CAP	Pathogenic	0.67	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	0.0	N
PhyloP100		6.9
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.32
MutPred		0.25		Loss of MoRF binding (P = 0.0155)
MVP		0.20
MPC		0.62
ClinPred		0.78	D
GERP RS		2.5
PromoterAI		0.082	Neutral
Varity_R		0.27
gMVP		0.42
Mutation Taster		=79/21	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: rs1744263423; hg19: chr5-60628110;