10-102862895-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136200.2(BORCS7):c.292C>G(p.Gln98Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000048 in 1,458,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: BORCS7 NM_001136200.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.68

Genes affected

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

BORCS7-ASMT (HGNC:):

ACMG classification

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=0.12588191).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BORCS7	NM_001136200.2	c.292C>G	p.Gln98Glu	missense_variant	5/5	ENST00000339834.10
BORCS7-ASMT	NR_037644.1	n.369C>G		non_coding_transcript_exon_variant	5/15
BORCS7	NM_144591.5	c.292C>G	p.Gln98Glu	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BORCS7	ENST00000339834.10	c.292C>G	p.Gln98Glu	missense_variant	5/5	1	NM_001136200.2	P1
BORCS7	ENST00000369883.3	c.292C>G	p.Gln98Glu	missense_variant	5/6	1		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000280 AC: 7 AN: 249844 Hom.: 0 AF XY: 0.0000222 AC XY: 3 AN XY: 135246

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000202

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000480 AC: 7 AN: 1458574 Hom.: 0 Cov.: 29 AF XY: 0.00000413 AC XY: 3 AN XY: 725860

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000157

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ExAC AF: 0.0000330 AC: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2022

The c.292C>G (p.Q98E) alteration is located in exon 5 (coding exon 5) of the BORCS7 gene. This alteration results from a C to G substitution at nucleotide position 292, causing the glutamine (Q) at amino acid position 98 to be replaced by a glutamic acid (E). 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	-0.19	T
BayesDel_noAF	Benign	-0.23
Cadd	Uncertain	24
Dann	Benign	0.84
Eigen	Benign	-0.059
Eigen_PC	Benign	0.10
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	D;D
PROVEAN	Benign	-0.36	N;N
REVEL	Benign	0.17
Sift	Benign	0.31	T;T
Sift4G	Benign	0.28	T;T
Vest4		0.32
MVP		0.28
MPC		0.20
ClinPred		0.11	T
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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

Other links and lift over

dbSNP: rs776954576; hg19: chr10-104622652;