7-99419434-C-G

Position:

• chr7-99419434-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003910.4(BUD31):​c.428C>G​(p.Ser143Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,498 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: BUD31 NM_003910.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.50

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]

PTCD1 (HGNC:22198): (pentatricopeptide repeat domain 1) This gene encodes a mitochondrial protein that binds leucine tRNAs and other mitochondrial RNAs and plays a role in the regulation of translation. Increased expression of this gene results in decreased mitochondrial leucine tRNA levels. Naturally occurring read-through transcription exists between upstream ATP5J2 (ATP synthase, H+ transporting, mitochondrial Fo complex, subunit F2) and this gene. [provided by RefSeq, Aug 2015]

ATP5MF-PTCD1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BUD31	NM_003910.4	c.428C>G	p.Ser143Cys	missense_variant	6/6	ENST00000222969.10	NP_003901.2
PTCD1	NM_015545.4	c.*533G>C		3_prime_UTR_variant	8/8	ENST00000292478.9	NP_056360.2
ATP5MF-PTCD1	NM_001198879.2	c.*533G>C		3_prime_UTR_variant	9/9		NP_001185808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BUD31	ENST00000222969.10	c.428C>G	p.Ser143Cys	missense_variant	6/6	1	NM_003910.4	ENSP00000222969	P1
PTCD1	ENST00000292478.9	c.*533G>C		3_prime_UTR_variant	8/8	1	NM_015545.4	ENSP00000292478	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459498 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726148

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 12, 2023

The c.428C>G (p.S143C) alteration is located in exon 6 (coding exon 4) of the BUD31 gene. This alteration results from a C to G substitution at nucleotide position 428, causing the serine (S) at amino acid position 143 to be replaced by a cysteine (C). 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	Uncertain	0.49
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.062	T;T;T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	.;D;D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.8	L;L;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.13
Sift	Uncertain	0.0080	D;D;D
Sift4G	Uncertain	0.015	D;D;D
Polyphen		0.054	B;B;.
Vest4		0.70
MutPred		0.62		Loss of phosphorylation at S143 (P = 0.0474);Loss of phosphorylation at S143 (P = 0.0474);.;
MVP		0.50
MPC		0.77
ClinPred		0.89	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.57
gMVP		0.78

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-99017057;