Genetic Variant UNC93A:p.Arg226* (chr6-167303969-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_018974.4(UNC93A):c.676C>T(p.Arg226*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00372 in 1,613,598 control chromosomes in the GnomAD database, including 19 homozygotes. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0027 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 15 hom. )

Consequence

UNC93A
NM_018974.4 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.433

Publications

15 publications found

Variant links:

Genes affected

UNC93A (HGNC:12570): (unc-93 homolog A) Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

UNC93A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 6-167303969-C-T is Benign according to our data. Variant chr6-167303969-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 773330.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018974.4. 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
	UNC93A	NM_018974.4	MANE Select	c.676C>T	p.Arg226*	stop_gained	Exon 5 of 8	NP_061847.2
	UNC93A	NM_001143947.2		c.550C>T	p.Arg184*	stop_gained	Exon 4 of 7	NP_001137419.1	Q86WB7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UNC93A	ENST00000230256.8	TSL:1 MANE Select	c.676C>T	p.Arg226*	stop_gained	Exon 5 of 8	ENSP00000230256.3	Q86WB7-1
UNC93A	ENST00000366829.2	TSL:1	c.550C>T	p.Arg184*	stop_gained	Exon 4 of 7	ENSP00000355794.2	Q86WB7-2
UNC93A	ENST00000860147.1		c.676C>T	p.Arg226*	stop_gained	Exon 6 of 9	ENSP00000530206.1

Frequencies

GnomAD3 genomes

AF:

0.00269

AC:

408

AN:

151590

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00611

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.0000952

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00365

Gnomad OTH

AF:

0.00626

GnomAD2 exomes

AF:

0.00240

AC:

597

AN:

249058

AF XY:

0.00239

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.00278

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00393

Gnomad OTH exome

AF:

0.00539

GnomAD4 exome

AF:

0.00383

AC:

5597

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00363

AC XY:

2643

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00114

AC:

AN:

33480

American (AMR)

AF:

0.00286

AC:

128

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000536

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000927

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000243

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00399

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00458

AC:

5089

AN:

1112008

Other (OTH)

AF:

0.00469

AC:

283

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

320

639

959

1278

1598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

200

400

600

800

1000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00268

AC:

407

AN:

151708

Hom.:

Cov.:

AF XY:

0.00281

AC XY:

208

AN XY:

74086

show subpopulations

African (AFR)

AF:

0.00107

AC:

AN:

41292

American (AMR)

AF:

0.00611

AC:

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000209

AC:

AN:

4782

European-Finnish (FIN)

AF:

0.0000952

AC:

AN:

10502

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00365

AC:

248

AN:

67952

Other (OTH)

AF:

0.00619

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.539

Heterozygous variant carriers

116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00353

Hom.:

Bravo

AF:

0.00321

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00326

AC:

ExAC

AF:

0.00236

AC:

286

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00491

EpiControl

AF:

0.00516

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.028

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.073

PhyloP100

0.43

Vest4

0.038

GERP RS

-2.7

Mutation Taster

=76/124

disease causing (fs/PTC)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over