chr10-56358605-T-C

Variant names:

• chr10-56358605-T-C
• rs1838232055
• NM_007057.4:c.743A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007057.4(ZWINT):​c.743A>G​(p.Glu248Gly) variant causes a missense 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZWINT NM_007057.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0890
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10545534).

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.743A>G	p.Glu248Gly	missense	Exon 7 of 9	NP_008988.2
	ZWINT	NM_032997.3		c.743A>G	p.Glu248Gly	missense	Exon 7 of 8	NP_127490.1	O95229-1
	ZWINT	NM_001005413.1		c.602A>G	p.Glu201Gly	missense	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.743A>G	p.Glu248Gly	missense	Exon 7 of 9	ENSP00000363055.3	O95229-1
	ZWINT	ENST00000318387.7	TSL:1	c.743A>G	p.Glu248Gly	missense	Exon 7 of 8	ENSP00000322850.3
	ZWINT	ENST00000920699.1		c.776A>G	p.Glu259Gly	missense	Exon 7 of 9	ENSP00000590758.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.089
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.057
Sift	Uncertain	0.0050	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.56	P
Vest4		0.26
MutPred		0.10		Loss of solvent accessibility (P = 0.1362)
MVP		0.18
MPC		0.36
ClinPred		0.70	D
GERP RS		-0.056
Varity_R		0.15
gMVP		0.057
Mutation Taster		=96/4	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: rs1838232055; hg19: chr10-58118366;