5-61435631-G-C

Variant names:

• chr5-61435631-G-C
• rs7709645
• NM_020928.2:c.677-37050G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020928.2(ZSWIM6):​c.677-37050G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 152,082 control chromosomes in the GnomAD database, including 28,989 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (28989 hom., cov: 33)
• Consequence: ZSWIM6 NM_020928.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20
• Publications: 22 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: STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM6	NM_020928.2	c.677-37050G>C		intron_variant	Intron 1 of 13	ENST00000252744.6	NP_065979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSWIM6	ENST00000252744.6	c.677-37050G>C		intron_variant	Intron 1 of 13	5	NM_020928.2	ENSP00000252744.5

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89407 AN: 151964 Hom.: 28920 Cov.: 33

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.554

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.589 AC: 89545 AN: 152082 Hom.: 28989 Cov.: 33 AF XY: 0.585 AC XY: 43507 AN XY: 74324

African (AFR) AF: 0.865 AC: 35920 AN: 41522

American (AMR) AF: 0.554 AC: 8461 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1527 AN: 3466

East Asian (EAS) AF: 0.202 AC: 1044 AN: 5178

South Asian (SAS) AF: 0.530 AC: 2557 AN: 4824

European-Finnish (FIN) AF: 0.472 AC: 4971 AN: 10528

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33254 AN: 67972

Other (OTH) AF: 0.559 AC: 1182 AN: 2114

Alfa AF: 0.488 Hom.: 10342

Bravo AF: 0.603

Asia WGS AF: 0.458 AC: 1594 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	19
DANN	Benign	0.67
PhyloP100		2.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs7709645; hg19: chr5-60731458;