chr10-102862887-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001136200.2(BORCS7):​c.284C>T​(p.Ser95Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000059 in 1,608,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000061 ( 0 hom. )

Consequence

BORCS7
NM_001136200.2 missense

Scores

4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.91
Variant links:
Genes affected
BORCS7 (HGNC:23516): (BLOC-1 related complex subunit 7) Part of BORC complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15484157).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BORCS7NM_001136200.2 linkuse as main transcriptc.284C>T p.Ser95Leu missense_variant 5/5 ENST00000339834.10
BORCS7-ASMTNR_037644.1 linkuse as main transcriptn.361C>T non_coding_transcript_exon_variant 5/15
BORCS7NM_144591.5 linkuse as main transcriptc.284C>T p.Ser95Leu missense_variant 5/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BORCS7ENST00000339834.10 linkuse as main transcriptc.284C>T p.Ser95Leu missense_variant 5/51 NM_001136200.2 P1
BORCS7ENST00000369883.3 linkuse as main transcriptc.284C>T p.Ser95Leu missense_variant 5/61 P1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152166
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000481
AC:
12
AN:
249706
Hom.:
0
AF XY:
0.0000666
AC XY:
9
AN XY:
135180
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000107
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000611
AC:
89
AN:
1456724
Hom.:
0
Cov.:
29
AF XY:
0.0000634
AC XY:
46
AN XY:
724998
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.0000759
Gnomad4 OTH exome
AF:
0.0000498
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152166
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000723
Hom.:
0
Bravo
AF:
0.0000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.00
EpiControl
AF:
0.000296

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 17, 2023The c.284C>T (p.S95L) alteration is located in exon 5 (coding exon 5) of the BORCS7 gene. This alteration results from a C to T substitution at nucleotide position 284, causing the serine (S) at amino acid position 95 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.29
CADD
Uncertain
25
DANN
Uncertain
0.98
Eigen
Benign
-0.13
Eigen_PC
Benign
-0.16
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.91
.;D
M_CAP
Benign
0.0084
T
MetaRNN
Benign
0.15
T;T
MetaSVM
Benign
-0.98
T
MutationTaster
Benign
1.0
N;N
PROVEAN
Uncertain
-2.4
N;N
REVEL
Benign
0.14
Sift
Benign
0.13
T;T
Sift4G
Benign
0.11
T;T
Vest4
0.35
MVP
0.34
MPC
0.16
ClinPred
0.15
T
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.18
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.

Other links and lift over

dbSNP: rs201496956; hg19: chr10-104622644; COSMIC: COSV100185906; COSMIC: COSV100185906; API