10-102862895-C-G

Variant names:

• chr10-102862895-C-G
• rs776954576
• NM_001136200.2:c.292C>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. 12/18 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
• Publications: 0 publications found

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:49183): (BORCS7-ASMT readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring C10orf32 (chromosome 10 open reading frame 32) and AS3MT (arsenic, +3 oxidation state, methyltransferase) genes. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is therefore unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

ENSG00000296999 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12588191).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136200.2. 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
	BORCS7	NM_001136200.2	MANE Select	c.292C>G	p.Gln98Glu	missense	Exon 5 of 5	NP_001129672.1	Q96B45
	BORCS7	NM_144591.5		c.292C>G	p.Gln98Glu	missense	Exon 5 of 6	NP_653192.2	Q96B45
	BORCS7-ASMT	NR_037644.1		n.369C>G		non_coding_transcript_exon	Exon 5 of 15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BORCS7	ENST00000339834.10	TSL:1 MANE Select	c.292C>G	p.Gln98Glu	missense	Exon 5 of 5	ENSP00000342331.5	Q96B45
	BORCS7	ENST00000369883.3	TSL:1	c.292C>G	p.Gln98Glu	missense	Exon 5 of 6	ENSP00000358899.3	Q96B45
	BORCS7-ASMT	ENST00000299353.6	TSL:5	n.292C>G		non_coding_transcript_exon	Exon 5 of 15	ENSP00000299353.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000280 AC: 7 AN: 249844 AF XY: 0.0000222

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 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

African (AFR) AF: 0.00 AC: 0 AN: 33420

American (AMR) AF: 0.000157 AC: 7 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108978

Other (OTH) AF: 0.00 AC: 0 AN: 60300

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.92	T
PhyloP100		4.7
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.17
Sift	Benign	0.31	T
Sift4G	Benign	0.28	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
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs776954576; hg19: chr10-104622652;