Genetic Variant NM_017622.3:c.341C>A (chr17-8189800-G-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_017622.3(BORCS6):c.341C>A(p.Ala114Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,593,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

BORCS6
NM_017622.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.677

Publications

0 publications found

Variant links:

Genes affected

BORCS6 (HGNC:25939): (BLOC-1 related complex subunit 6) Enables identical protein binding activity. Involved in lysosome localization. Part of BORC complex. [provided by Alliance of Genome Resources, Apr 2022]

BORCS6 links:

ENSG00000299228 (HGNC:):

ENSG00000299228 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.02911526).

BP6

Variant 17-8189800-G-T is Benign according to our data. Variant chr17-8189800-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3134779.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017622.3. 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
	BORCS6	NM_017622.3	MANE Select	c.341C>A	p.Ala114Glu	missense	Exon 1 of 1	NP_060092.2	Q96GS4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BORCS6	ENST00000389017.6	TSL:6 MANE Select	c.341C>A	p.Ala114Glu	missense	Exon 1 of 1	ENSP00000373669.4	Q96GS4
ENSG00000299228	ENST00000761712.1		n.317G>T		non_coding_transcript_exon	Exon 1 of 1
ENSG00000279152	ENST00000622992.1	TSL:6	n.*112G>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000637

AC:

AN:

204124

AF XY:

0.0000700

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000948

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000112

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000111

AC:

160

AN:

1440982

Hom.:

Cov.:

AF XY:

0.000112

AC XY:

AN XY:

716724

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33046

American (AMR)

AF:

0.000117

AC:

AN:

42918

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25878

East Asian (EAS)

AF:

0.00

AC:

AN:

39068

South Asian (SAS)

AF:

0.00

AC:

AN:

85164

European-Finnish (FIN)

AF:

0.0000235

AC:

AN:

42504

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.000136

AC:

151

AN:

1106956

Other (OTH)

AF:

0.0000502

AC:

AN:

59718

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41454

American (AMR)

AF:

0.000131

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

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:

0.000117

Hom.:

Bravo

AF:

0.0000982

ExAC

AF:

0.0000341

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.60

CADD

Benign

5.4

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.0049

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0070

LIST_S2

Benign

0.31

M_CAP

Benign

0.0037

MetaRNN

Benign

0.029

MetaSVM

Benign

-1.0

PhyloP100

0.68

PROVEAN

Benign

0.48

REVEL

Benign

0.061

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.062

MVP

0.014

ClinPred

0.064

GERP RS

1.4

PromoterAI

0.027

Neutral

(source)

Varity_R

0.040

gMVP

0.046

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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