rs387907123

Positions:

• chr10-58702095-C-A
• chr10-58702095-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001080512.3(BICC1):​c.259C>A​(p.Gln87Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BICC1 NM_001080512.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.60

Genes affected

BICC1 (HGNC:19351): (BicC family RNA binding protein 1) This gene encodes an RNA-binding protein that is active in regulating gene expression by modulating protein translation during embryonic development. Mouse studies identified the corresponding protein to be under strict control during cell differentiation and to be a maternally provided gene product. [provided by RefSeq, Apr 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.749

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BICC1	NM_001080512.3	c.259C>A	p.Gln87Lys	missense_variant	3/21	ENST00000373886.8	NP_001073981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BICC1	ENST00000373886.8	c.259C>A	p.Gln87Lys	missense_variant	3/21	1	NM_001080512.3	ENSP00000362993.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250406 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135322

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460884 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726694

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	0.0025	T
BayesDel_noAF	Benign	-0.13
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.070	T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.0087	T
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.12
Sift	Benign	0.26	T
Sift4G	Benign	0.27	T
Polyphen		0.92	P
Vest4		0.86
MutPred		0.35		Gain of ubiquitination at Q87 (P = 0.0267);
MVP		0.69
MPC		0.28
ClinPred		0.56	D
GERP RS		5.8
Varity_R		0.54
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs387907123; hg19: chr10-60461855;