Genetic Variant LOC101930434:p.Ile73Thr (chr15-30801393-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The XM_017022809.1(LOC101930434):c.218T>C(p.Ile73Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0036 in 149,552 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 3 hom., cov: 28)

Exomes 𝑓: 0.00074 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

LOC101930434
XM_017022809.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.59

Publications

0 publications found

Variant links:

Genes affected

LOC101930434 (HGNC:):

LOC101930434 links:

GOLGA8UP (HGNC:44411): (golgin A8 family member U, pseudogene)

GOLGA8UP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 15-30801393-T-C is Benign according to our data. Variant chr15-30801393-T-C is described in ClinVar as Benign. ClinVar VariationId is 2645109.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000527159.2. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
GOLGA8UP	ENST00000527159.2	TSL:6	n.1469T>C	non_coding_transcript_exon	Exon 17 of 19
ENSG00000307355	ENST00000825370.1		n.105+8A>G	splice_region intron	N/A
ENSG00000307338	ENST00000825164.1		n.-46T>C	upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.00360

AC:

538

AN:

149432

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0102

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00159

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000389

Gnomad SAS

AF:

0.000836

Gnomad FIN

AF:

0.00116

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00102

Gnomad OTH

AF:

0.00441

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000743

AC:

1075

AN:

1447648

Hom.:

Cov.:

AF XY:

0.000716

AC XY:

515

AN XY:

719590

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0108

AC:

361

AN:

33404

American (AMR)

AF:

0.000608

AC:

AN:

44376

Ashkenazi Jewish (ASJ)

AF:

0.0000386

AC:

AN:

25888

East Asian (EAS)

AF:

0.000504

AC:

AN:

39692

South Asian (SAS)

AF:

0.000770

AC:

AN:

85678

European-Finnish (FIN)

AF:

0.00143

AC:

AN:

48304

Middle Eastern (MID)

AF:

0.000182

AC:

AN:

5480

European-Non Finnish (NFE)

AF:

0.000402

AC:

444

AN:

1104876

Other (OTH)

AF:

0.00143

AC:

AN:

59950

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.381

Heterozygous variant carriers

112

149

186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.00360

AC:

538

AN:

149552

Hom.:

Cov.:

AF XY:

0.00338

AC XY:

247

AN XY:

73066

show subpopulations

African (AFR)

AF:

0.0102

AC:

418

AN:

41132

American (AMR)

AF:

0.00159

AC:

AN:

15090

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3424

East Asian (EAS)

AF:

0.000390

AC:

AN:

5128

South Asian (SAS)

AF:

0.000836

AC:

AN:

4782

European-Finnish (FIN)

AF:

0.00116

AC:

AN:

10324

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00102

AC:

AN:

66404

Other (OTH)

AF:

0.00436

AC:

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00533

Hom.:

ClinVar

ClinVar submissions

Significance: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_noAF

Benign

-0.61

CADD

Benign

4.1

(source)

DANN

Benign

0.34

PhyloP100

3.6

Splicing

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