Variant 12-120071625-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001367886.1(BICDL1):c.913C>T(p.His305Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,452,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

BICDL1
NM_001367886.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.91

Variant links:

Genes affected

BICDL1 (HGNC:28095): (BICD family like cargo adaptor 1) Predicted to enable dynactin binding activity and small GTPase binding activity. Predicted to be involved in Golgi to secretory granule transport; neuron projection development; and vesicle transport along microtubule. Predicted to be located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

BICDL1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2782179).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BICDL1	NM_001367886.1 linkuse as main transcript	c.913C>T	p.His305Tyr	missense_variant	5/10	ENST00000548673.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BICDL1	ENST00000548673.6 linkuse as main transcript	c.913C>T	p.His305Tyr	missense_variant	5/10	2	NM_001367886.1	A1
BICDL1	ENST00000546420.5 linkuse as main transcript	c.*385C>T		3_prime_UTR_variant, NMD_transcript_variant	6/9	1
BICDL1	ENST00000397558.6 linkuse as main transcript	c.913C>T	p.His305Tyr	missense_variant	5/9	5		P4	Q6ZP65-1
BICDL1	ENST00000546790.1 linkuse as main transcript	n.247C>T		non_coding_transcript_exon_variant	2/3	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000416

AC:

AN:

240278

Hom.:

AF XY:

0.00000765

AC XY:

AN XY:

130644

show subpopulations

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000910

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1452488

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722370

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2021

The c.913C>T (p.H305Y) alteration is located in exon 5 (coding exon 5) of the BICDL1 gene. This alteration results from a C to T substitution at nucleotide position 913, causing the histidine (H) at amino acid position 305 to be replaced by a tyrosine (Y). 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

0.11

BayesDel_addAF

Uncertain

0.034

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.081

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.029

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.43

MutationTaster

Benign

0.52

D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.9

REVEL

Benign

0.12

Sift

Uncertain

0.017

Sift4G

Benign

1.0

Polyphen

0.91

Vest4

0.50

MutPred

0.094

Gain of phosphorylation at H305 (P = 0.1459);

MVP

0.17

MPC

1.3

ClinPred

0.74

GERP RS

5.7

Varity_R

0.18

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over