10-97499250-C-A

Variant names:

• chr10-97499250-C-A
• rs2040299951
• NM_024954.5:c.47C>A
• UBTD1 p.Pro16Gln

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024954.5(UBTD1):​c.47C>A​(p.Pro16Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P16R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UBTD1 NM_024954.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 0 publications found

Genes affected

UBTD1 (HGNC:25683): (ubiquitin domain containing 1) The degradation of many proteins is carried out by the ubiquitin pathway in which proteins are targeted for degradation by covalent conjugation of the polypeptide ubiquitin. This gene encodes a protein that belongs to the ubiquitin family of proteins. The encoded protein is thought to regulate E2 ubiquitin conjugating enzymes belonging to the UBE2D family. [provided by RefSeq, Mar 2014]

MMS19 (HGNC:13824): (MMS19 homolog, cytosolic iron-sulfur assembly component) Enables estrogen receptor binding activity and transcription coactivator activity. Involved in several processes, including iron-sulfur cluster assembly; positive regulation of nucleobase-containing compound metabolic process; and protein maturation by iron-sulfur cluster transfer. Located in cytosol; nucleoplasm; and spindle. Part of CIA complex and MMXD complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08023271).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024954.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBTD1	NM_024954.5	MANE Select	c.47C>A	p.Pro16Gln	missense	Exon 1 of 3	NP_079230.1	Q9HAC8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBTD1	ENST00000370664.4	TSL:1 MANE Select	c.47C>A	p.Pro16Gln	missense	Exon 1 of 3	ENSP00000359698.3	Q9HAC8
	UBTD1	ENST00000958439.1		c.47C>A	p.Pro16Gln	missense	Exon 1 of 4	ENSP00000628498.1
	UBTD1	ENST00000923989.1		c.47C>A	p.Pro16Gln	missense	Exon 1 of 2	ENSP00000594048.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1396210 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 688632

African (AFR) AF: 0.00 AC: 0 AN: 31248

American (AMR) AF: 0.00 AC: 0 AN: 35422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25114

East Asian (EAS) AF: 0.00 AC: 0 AN: 35508

South Asian (SAS) AF: 0.00 AC: 0 AN: 78758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49024

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5522

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1077750

Other (OTH) AF: 0.00 AC: 0 AN: 57864

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.55	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.1
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	0.27	N
REVEL	Benign	0.056
Sift	Benign	0.49	T
Sift4G	Benign	0.68	T
PromoterAI		-0.013	Neutral
Varity_R		0.16
gMVP		0.36
Mutation Taster		=81/19	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2040299951;

hg19: chr10-99259007;