Variant 5-61332312-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_ModerateBP6_ModerateBS2

The NM_020928.2(ZSWIM6):c.40C>T(p.Leu14Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000006 in 1,167,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

ZSWIM6
NM_020928.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.92

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ZSWIM6. . Gene score misZ 4.1751 (greater than the threshold 3.09). Trascript score misZ 3.277 (greater than threshold 3.09). GenCC has associacion of gene with acromelic frontonasal dysostosis, neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features.

BP4

Computational evidence support a benign effect (MetaRNN=0.18052235).

BP6

Variant 5-61332312-C-T is Benign according to our data. Variant chr5-61332312-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1567210.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZSWIM6	NM_020928.2 linkuse as main transcript	c.40C>T	p.Leu14Phe	missense_variant	1/14	ENST00000252744.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZSWIM6	ENST00000252744.6 linkuse as main transcript	c.40C>T	p.Leu14Phe	missense_variant	1/14	5	NM_020928.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150274

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000492

AC:

AN:

1016942

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

481652

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000455

Gnomad4 OTH exome

AF:

0.0000257

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150274

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73354

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 06, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0038

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.73

M_CAP

Pathogenic

0.57

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.77

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.57

REVEL

Benign

0.071

Sift

Benign

0.067

Sift4G

Benign

0.39

Polyphen

0.51

Vest4

0.14

MutPred

0.42

Gain of sheet (P = 0.0827);

MVP

0.10

MPC

0.54

ClinPred

0.28

GERP RS

0.38

Varity_R

0.082

gMVP

0.42

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over