Genetic Variant MIS18A:p.Val151Val (chr21-32270478-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_018944.3(MIS18A):c.453G>A(p.Val151Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000262 in 1,609,816 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00018 ( 2 hom. )

Consequence

MIS18A
NM_018944.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.08

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 21-32270478-C-T is Benign according to our data. Variant chr21-32270478-C-T is described in ClinVar as [Benign]. Clinvar id is 778903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.08 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIS18A	NM_018944.3 link	c.453G>A	p.Val151Val	synonymous_variant	Exon 3 of 5	ENST00000290130.4	NP_061817.1	Q9NYP9
MIS18A	XM_017028400.2 link	c.453G>A	p.Val151Val	synonymous_variant	Exon 3 of 5		XP_016883889.1
MIS18A	XM_017028401.2 link	c.453G>A	p.Val151Val	synonymous_variant	Exon 3 of 5		XP_016883890.1
MIS18A	XR_002958619.2 link	n.488G>A		non_coding_transcript_exon_variant	Exon 3 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIS18A	ENST00000290130.4 link	c.453G>A	p.Val151Val	synonymous_variant	Exon 3 of 5	1	NM_018944.3	ENSP00000290130.3		Q9NYP9
MIS18A	ENST00000486363.1 link	n.101G>A		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.00105

AC:

160

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00319

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.000276

AC:

AN:

246566

AF XY:

0.000195

show subpopulations

Gnomad AFR exome

AF:

0.00304

Gnomad AMR exome

AF:

0.000239

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000893

Gnomad OTH exome

AF:

0.000334

GnomAD4 exome

AF:

0.000178

AC:

260

AN:

1457586

Hom.:

Cov.:

AF XY:

0.000172

AC XY:

125

AN XY:

725182

show subpopulations

African (AFR)

AF:

0.00435

AC:

144

AN:

33128

American (AMR)

AF:

0.000457

AC:

AN:

43780

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26026

East Asian (EAS)

AF:

0.00

AC:

AN:

39450

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85548

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53346

Middle Eastern (MID)

AF:

0.00209

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.0000450

AC:

AN:

1110346

Other (OTH)

AF:

0.000548

AC:

AN:

60216

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00106

AC:

162

AN:

152230

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00320

AC:

133

AN:

41534

American (AMR)

AF:

0.00137

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68030

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000586

Hom.:

Bravo

AF:

0.00140

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 30, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.36

(source)

DANN

Benign

0.55

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism

(source)

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

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chr21-32270478-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over