10-102862162-A-G

Variant names:

• chr10-102862162-A-G
• NM_001136200.2:c.251A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001136200.2(BORCS7):​c.251A>G​(p.Gln84Arg) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BORCS7 NM_001136200.2 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.61
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BORCS7	NM_001136200.2	c.251A>G	p.Gln84Arg	missense_variant, splice_region_variant	Exon 4 of 5	ENST00000339834.10	NP_001129672.1
BORCS7	NM_144591.5	c.251A>G	p.Gln84Arg	missense_variant, splice_region_variant	Exon 4 of 6		NP_653192.2
BORCS7-ASMT	NR_037644.1	n.328A>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 4 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BORCS7	ENST00000339834.10	c.251A>G	p.Gln84Arg	missense_variant, splice_region_variant	Exon 4 of 5	1	NM_001136200.2	ENSP00000342331.5
BORCS7	ENST00000369883.3	c.251A>G	p.Gln84Arg	missense_variant, splice_region_variant	Exon 4 of 6	1		ENSP00000358899.3
BORCS7-ASMT	ENST00000299353.6	n.251A>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 4 of 15	5		ENSP00000299353.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.251A>G (p.Q84R) alteration is located in exon 4 (coding exon 4) of the BORCS7 gene. This alteration results from a A to G substitution at nucleotide position 251, causing the glutamine (Q) at amino acid position 84 to be replaced by an arginine (R). 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	Pathogenic	0.61
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.78	.;T
M_CAP	Benign	0.0051	T
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-0.69	T
PhyloP100		7.6
PROVEAN	Benign	-0.84	N;N
REVEL	Benign	0.22
Sift	Benign	0.34	T;T
Sift4G	Benign	0.21	T;T
Vest4		0.68
MVP		0.46
MPC		0.21
ClinPred		0.69	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.58
Mutation Taster		=57/43	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr10-104621919;