10-102854396-A-G

Position:

• chr10-102854396-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001136200.2(BORCS7):​c.110A>G​(p.Lys37Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: BORCS7 NM_001136200.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.82

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]

ENSG00000282772 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060058862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BORCS7	NM_001136200.2	c.110A>G	p.Lys37Arg	missense_variant	1/5	ENST00000339834.10	NP_001129672.1
BORCS7	NM_144591.5	c.110A>G	p.Lys37Arg	missense_variant	1/6		NP_653192.2
BORCS7-ASMT	NR_037644.1	n.187A>G		non_coding_transcript_exon_variant	1/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BORCS7	ENST00000339834.10	c.110A>G	p.Lys37Arg	missense_variant	1/5	1	NM_001136200.2	ENSP00000342331.5
BORCS7-ASMT	ENST00000299353.6	n.110A>G		non_coding_transcript_exon_variant	1/15	5		ENSP00000299353.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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

Jul 06, 2024

The c.110A>G (p.K37R) alteration is located in exon 1 (coding exon 1) of the BORCS7 gene. This alteration results from a A to G substitution at nucleotide position 110, causing the lysine (K) at amino acid position 37 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	Benign	0.070
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Benign	0.85
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.83	.;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.060	T;T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	1.7	N;N
REVEL	Benign	0.053
Sift	Benign	1.0	T;T
Sift4G	Benign	0.92	T;T
Vest4		0.21
MVP		0.23
MPC		0.13
ClinPred		0.16	T
GERP RS		4.8
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-104614153;