UBTFL1 p.Met125Ile

Variant names:

• chr11-90086324-G-T
• NM_001143975.1:c.375G>T
• UBTFL1 p.Met125Ile

Your query was ambiguous. Multiple possible variants found:

• chr11-90086324-G-T
• chr11-90086324-G-C
• chr11-90086324-G-A

Variant summary

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

The NM_001143975.1(UBTFL1):​c.375G>T​(p.Met125Ile) 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. 9/13 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UBTFL1 NM_001143975.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.55
• Publications: 0 publications found

Genes affected

UBTFL1 (HGNC:14533): (upstream binding transcription factor like 1) Predicted to enable DNA binding activity. Predicted to act upstream of or within blastocyst growth; embryo implantation; and regulation of gene expression. Predicted to be located in cytoplasm and nucleus. [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=0.17022195).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143975.1. 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
	UBTFL1	NM_001143975.1	MANE Select	c.375G>T	p.Met125Ile	missense	Exon 1 of 1	NP_001137447.1	P0CB47

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBTFL1	ENST00000530464.2	TSL:6 MANE Select	c.375G>T	p.Met125Ile	missense	Exon 1 of 1	ENSP00000485108.1	P0CB47

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.30e-7 AC: 1 AN: 1369922 Hom.: 0 Cov.: 31 AF XY: 0.00000147 AC XY: 1 AN XY: 682458

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32320

American (AMR) AF: 0.00 AC: 0 AN: 31158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25464

East Asian (EAS) AF: 0.00 AC: 0 AN: 34610

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47792

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5518

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1054556

Other (OTH) AF: 0.00 AC: 0 AN: 57384

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.00015	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	5.1
DANN	Benign	0.55
DEOGEN2	Uncertain	0.54	D
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.17	T
MutationAssessor	Benign	0.67	N
PhyloP100		3.5
PrimateAI	Uncertain	0.54	T
Sift4G	Benign	0.12	T
PromoterAI		0.0078	Neutral
Varity_R		0.41
gMVP		0.21

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

hg19: chr11-89819492;