10-56358870-G-A

Variant names:

• chr10-56358870-G-A
• rs149984887
• NM_007057.4:c.558C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_007057.4(ZWINT):​c.558C>T​(p.Asp186Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 1,614,016 control chromosomes in the GnomAD database, including 3 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 0.00019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (3 hom.)
• Consequence: ZWINT NM_007057.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.64
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-2.64 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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.558C>T	p.Asp186Asp	synonymous	Exon 6 of 9	NP_008988.2
	ZWINT	NM_032997.3		c.558C>T	p.Asp186Asp	synonymous	Exon 6 of 8	NP_127490.1	O95229-1
	ZWINT	NM_001005413.1		c.519+39C>T		intron	N/A	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.558C>T	p.Asp186Asp	synonymous	Exon 6 of 9	ENSP00000363055.3	O95229-1
	ZWINT	ENST00000318387.7	TSL:1	c.558C>T	p.Asp186Asp	synonymous	Exon 6 of 8	ENSP00000322850.3
	ZWINT	ENST00000920699.1		c.591C>T	p.Asp197Asp	synonymous	Exon 6 of 9	ENSP00000590758.1

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152074 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000338 AC: 85 AN: 251164 AF XY: 0.000412

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000529

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000170 AC: 249 AN: 1461824 Hom.: 3 Cov.: 35 AF XY: 0.000219 AC XY: 159 AN XY: 727214

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.000358 AC: 16 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00187 AC: 161 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000414 AC: 46 AN: 1111986

Other (OTH) AF: 0.000397 AC: 24 AN: 60396

GnomAD4 genome AF: 0.000191 AC: 29 AN: 152192 Hom.: 0 Cov.: 32 AF XY: 0.000282 AC XY: 21 AN XY: 74402

African (AFR) AF: 0.0000241 AC: 1 AN: 41530

American (AMR) AF: 0.000262 AC: 4 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5162

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68004

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.000128

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.93
DANN	Benign	0.32
PhyloP100		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs149984887; hg19: chr10-58118631;