Variant 21-32270481-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_018944.3(MIS18A):c.450C>T(p.Tyr150Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,608,694 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0070 ( 15 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 11 hom. )

Consequence

MIS18A
NM_018944.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0240

Variant links:

Genes affected

MIS18A (HGNC:1286): (MIS18 kinetochore protein A) Enables identical protein binding activity. Predicted to be involved in CENP-A containing chromatin assembly and chromosome segregation. Predicted to act upstream of or within regulation of DNA methylation. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MIS18A links:

MIS18A (HGNC:):

MIS18A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 21-32270481-G-A is Benign according to our data. Variant chr21-32270481-G-A is described in ClinVar as [Benign]. Clinvar id is 709799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.024 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00699 (1064/152200) while in subpopulation AFR AF= 0.0232 (963/41504). AF 95% confidence interval is 0.022. There are 15 homozygotes in gnomad4. There are 503 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIS18A	NM_018944.3 linkuse as main transcript	c.450C>T	p.Tyr150Tyr	synonymous_variant	3/5	ENST00000290130.4	NP_061817.1	Q9NYP9
MIS18A	XM_017028400.2 linkuse as main transcript	c.450C>T	p.Tyr150Tyr	synonymous_variant	3/5		XP_016883889.1
MIS18A	XM_017028401.2 linkuse as main transcript	c.450C>T	p.Tyr150Tyr	synonymous_variant	3/5		XP_016883890.1
MIS18A	XR_002958619.2 linkuse as main transcript	n.485C>T		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIS18A	ENST00000290130.4 linkuse as main transcript	c.450C>T	p.Tyr150Tyr	synonymous_variant	3/5	1	NM_018944.3	ENSP00000290130.3		Q9NYP9
MIS18A	ENST00000486363.1 linkuse as main transcript	n.98C>T		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.00698

AC:

1062

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0232

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00200

AC:

490

AN:

244412

Hom.:

AF XY:

0.00164

AC XY:

217

AN XY:

132488

show subpopulations

Gnomad AFR exome

AF:

0.0248

Gnomad AMR exome

AF:

0.00155

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000564

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000369

Gnomad OTH exome

AF:

0.00186

GnomAD4 exome

AF:

0.00103

AC:

1495

AN:

1456494

Hom.:

Cov.:

AF XY:

0.000919

AC XY:

666

AN XY:

724700

show subpopulations

Gnomad4 AFR exome

AF:

0.0241

Gnomad4 AMR exome

AF:

0.00179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.0000351

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000416

Gnomad4 OTH exome

AF:

0.00234

GnomAD4 genome

AF:

0.00699

AC:

1064

AN:

152200

Hom.:

Cov.:

AF XY:

0.00676

AC XY:

503

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0232

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00390

Hom.:

Bravo

AF:

0.00828

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.5

DANN

Benign

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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