10-102854366-C-T

Variant names:

• chr10-102854366-C-T
• rs767070482
• NM_001136200.2:c.80C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001136200.2(BORCS7):​c.80C>T​(p.Thr27Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000117 in 1,578,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: BORCS7 NM_001136200.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.31
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13305357).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BORCS7	NM_001136200.2	c.80C>T	p.Thr27Ile	missense_variant	Exon 1 of 5	ENST00000339834.10	NP_001129672.1
BORCS7	NM_144591.5	c.80C>T	p.Thr27Ile	missense_variant	Exon 1 of 6		NP_653192.2
BORCS7-ASMT	NR_037644.1	n.157C>T		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.80C>T	p.Thr27Ile	missense_variant	Exon 1 of 5	1	NM_001136200.2	ENSP00000342331.5
BORCS7-ASMT	ENST00000299353.6	n.80C>T		non_coding_transcript_exon_variant	Exon 1 of 15	5		ENSP00000299353.5

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152056 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000961

GnomAD2 exomes AF: 0.000129 AC: 25 AN: 193262 AF XY: 0.0000876

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000327

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000134

Gnomad OTH exome AF: 0.000197

GnomAD4 exome AF: 0.000119 AC: 170 AN: 1426560 Hom.: 0 Cov.: 30 AF XY: 0.000105 AC XY: 74 AN XY: 705960

African (AFR) AF: 0.0000906 AC: 3 AN: 33106

American (AMR) AF: 0.000284 AC: 11 AN: 38798

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25404

East Asian (EAS) AF: 0.00 AC: 0 AN: 38600

South Asian (SAS) AF: 0.0000980 AC: 8 AN: 81618

European-Finnish (FIN) AF: 0.0000197 AC: 1 AN: 50770

Middle Eastern (MID) AF: 0.00385 AC: 22 AN: 5714

European-Non Finnish (NFE) AF: 0.000103 AC: 113 AN: 1093372

Other (OTH) AF: 0.000203 AC: 12 AN: 59178

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152056 Hom.: 0 Cov.: 31 AF XY: 0.0000943 AC XY: 7 AN XY: 74262

African (AFR) AF: 0.00 AC: 0 AN: 41400

American (AMR) AF: 0.000459 AC: 7 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00316 AC: 1 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68032

Other (OTH) AF: 0.000961 AC: 2 AN: 2082

Alfa AF: 0.000183 Hom.: 0

Bravo AF: 0.000151

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ExAC AF: 0.0000834 AC: 10

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.80C>T (p.T27I) alteration is located in exon 1 (coding exon 1) of the BORCS7 gene. This alteration results from a C to T substitution at nucleotide position 80, causing the threonine (T) at amino acid position 27 to be replaced by an isoleucine (I). 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	0.15
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	26
DANN	Uncertain	0.99
Eigen	Benign	0.051
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.80	.;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.87	T
PhyloP100		5.3
PROVEAN	Benign	-0.44	N;N
REVEL	Benign	0.049
Sift	Benign	0.079	T;T
Sift4G	Benign	0.068	T;T
Vest4		0.36
MVP		0.46
MPC		0.18
ClinPred		0.11	T
GERP RS		5.9
PromoterAI		0.089	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
gMVP		0.27
Mutation Taster		=61/39	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs767070482; hg19: chr10-104614123;