10-56358655-C-T

Variant names:

• chr10-56358655-C-T
• rs746108097
• NM_007057.4:c.693G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_007057.4(ZWINT):​c.693G>A​(p.Glu231Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: ZWINT NM_007057.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116
• Publications: 0 publications found

Genes affected

ZWINT (HGNC:13195): (ZW10 interacting kinetochore protein) This gene encodes a protein that is clearly involved in kinetochore function although an exact role is not known. It interacts with ZW10, another kinetochore protein, possibly regulating the association between ZW10 and kinetochores. The encoded protein localizes to prophase kinetochores before ZW10 does and it remains detectable on the kinetochore until late anaphase. It has a uniform distribution in the cytoplasm of interphase cells. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=-0.116 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007057.4. 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
	ZWINT	NM_007057.4	MANE Select	c.693G>A	p.Glu231Glu	synonymous	Exon 7 of 9	NP_008988.2
	ZWINT	NM_032997.3		c.693G>A	p.Glu231Glu	synonymous	Exon 7 of 8	NP_127490.1	O95229-1
	ZWINT	NM_001005413.1		c.552G>A	p.Glu184Glu	synonymous	Exon 7 of 9	NP_001005413.1	O95229-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZWINT	ENST00000373944.8	TSL:1 MANE Select	c.693G>A	p.Glu231Glu	synonymous	Exon 7 of 9	ENSP00000363055.3	O95229-1
	ZWINT	ENST00000318387.7	TSL:1	c.693G>A	p.Glu231Glu	synonymous	Exon 7 of 8	ENSP00000322850.3
	ZWINT	ENST00000920699.1		c.726G>A	p.Glu242Glu	synonymous	Exon 7 of 9	ENSP00000590758.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251372 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.99
DANN	Benign	0.31
PhyloP100		-0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs746108097; hg19: chr10-58118416;