chr10-102854416-C-G

Variant names:

• chr10-102854416-C-G
• rs901588590
• NM_001136200.2:c.130C>G

Variant summary

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

The NM_001136200.2(BORCS7):​c.130C>G​(p.Arg44Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000721 in 1,387,568 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R44W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: BORCS7 NM_001136200.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.82
• 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]

ENSG00000282772 (HGNC:):

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.130C>G	p.Arg44Gly	missense_variant	Exon 1 of 5	ENST00000339834.10	NP_001129672.1
BORCS7	NM_144591.5	c.130C>G	p.Arg44Gly	missense_variant	Exon 1 of 6		NP_653192.2
BORCS7-ASMT	NR_037644.1	n.207C>G		non_coding_transcript_exon_variant	Exon 1 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BORCS7	ENST00000339834.10	c.130C>G	p.Arg44Gly	missense_variant	Exon 1 of 5	1	NM_001136200.2	ENSP00000342331.5
BORCS7-ASMT	ENST00000299353.6	n.130C>G		non_coding_transcript_exon_variant	Exon 1 of 15	5		ENSP00000299353.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.21e-7 AC: 1 AN: 1387568 Hom.: 0 Cov.: 30 AF XY: 0.00000147 AC XY: 1 AN XY: 681060

African (AFR) AF: 0.00 AC: 0 AN: 31652

American (AMR) AF: 0.00 AC: 0 AN: 35596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25078

East Asian (EAS) AF: 0.00 AC: 0 AN: 35688

South Asian (SAS) AF: 0.00 AC: 0 AN: 79110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49138

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5444

European-Non Finnish (NFE) AF: 9.36e-7 AC: 1 AN: 1068480

Other (OTH) AF: 0.00 AC: 0 AN: 57382

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	28
DANN	Uncertain	1.0
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	.;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-0.74	T
PhyloP100		6.8
PROVEAN	Pathogenic	-5.3	D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.017	D;D
Vest4		0.87
MVP		0.38
MPC		0.40
ClinPred		0.99	D
GERP RS		5.0
PromoterAI		-0.0085	Neutral
gMVP		0.43
Mutation Taster		=57/43	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs901588590; hg19: chr10-104614173;