Variant chr7-99411178-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_003910.4(BUD31):c.86T>C(p.Met29Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BUD31
NM_003910.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.46

Variant links:

Genes affected

BUD31 (HGNC:29629): (BUD31 homolog) Enables nuclear receptor binding activity and nuclear receptor coactivator activity. Involved in mRNA splicing, via spliceosome and positive regulation of androgen receptor activity. Located in nucleus. Part of U2-type catalytic step 2 spliceosome. Colocalizes with chromatin. [provided by Alliance of Genome Resources, Apr 2022]

BUD31 links:

BUD31 (HGNC:):

BUD31 links:

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ACMG classification

Classification made for transcript

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, 0.836

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BUD31	NM_003910.4 linkuse as main transcript	c.86T>C	p.Met29Thr	missense_variant	3/6	ENST00000222969.10	NP_003901.2	P41223-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BUD31	ENST00000222969.10 linkuse as main transcript	c.86T>C	p.Met29Thr	missense_variant	3/6	1	NM_003910.4	ENSP00000222969.5		P41223-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250868

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135606

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461228

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726898

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 24, 2022

The c.86T>C (p.M29T) alteration is located in exon 3 (coding exon 1) of the BUD31 gene. This alteration results from a T to C substitution at nucleotide position 86, causing the methionine (M) at amino acid position 29 to be replaced by a threonine (T). 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

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.39

BayesDel_noAF

Pathogenic

0.41

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

T;T;T

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

.;D;D

M_CAP

Benign

0.028

MetaRNN

Pathogenic

0.84

D;D;D

MetaSVM

Uncertain

-0.18

MutationAssessor

Pathogenic

3.6

H;H;.

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-5.6

D;D;D

REVEL

Uncertain

0.56

Sift

Pathogenic

0.0

D;D;D

Sift4G

Benign

0.067

T;T;T

Polyphen

0.45

B;B;.

Vest4

0.82

MutPred

0.70

Gain of glycosylation at M29 (P = 0.0118);Gain of glycosylation at M29 (P = 0.0118);Gain of glycosylation at M29 (P = 0.0118);

MVP

0.60

MPC

1.3

ClinPred

0.99

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.95

gMVP

0.89

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

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