NM_001143975.1:c.375G>C

Variant names:

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

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>C​(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)
• 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=0.17021304).

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>C	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>C	p.Met125Ile	missense	Exon 1 of 1	ENSP00000485108.1	P0CB47

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

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	5.0
DANN	Benign	0.61
DEOGEN2	Uncertain	0.54	D
FATHMM_MKL	Benign	0.65	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		0.0084	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;