5-61332278-G-C

Variant names:

• chr5-61332278-G-C
• rs1043448103
• NM_020928.2:c.6G>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP7 BS2

The NM_020928.2(ZSWIM6):​c.6G>C​(p.Ala2Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000788 in 1,014,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A2A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000079 (0 hom.)
• Consequence: ZSWIM6 NM_020928.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP7: Synonymous conserved (PhyloP=1.76 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 8 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.6G>C	p.Ala2Ala	synonymous	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.6G>C	p.Ala2Ala	synonymous	Exon 1 of 14	ENSP00000252744.5	Q9HCJ5
	ENSG00000288936	ENST00000821437.1		n.71C>G		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000288936	ENST00000821446.1		n.61C>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000788 AC: 8 AN: 1014754 Hom.: 0 Cov.: 28 AF XY: 0.00000836 AC XY: 4 AN XY: 478448

African (AFR) AF: 0.00 AC: 0 AN: 20672

American (AMR) AF: 0.00 AC: 0 AN: 6010

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11602

East Asian (EAS) AF: 0.00 AC: 0 AN: 21470

South Asian (SAS) AF: 0.00 AC: 0 AN: 18996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3784

European-Non Finnish (NFE) AF: 0.00000799 AC: 7 AN: 876388

Other (OTH) AF: 0.0000257 AC: 1 AN: 38900

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	15
DANN	Benign	0.66
PhyloP100		1.8
PromoterAI		-0.20	Neutral

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: rs1043448103; hg19: chr5-60628105;