chr11-90086409-C-T

Variant names:

• chr11-90086409-C-T
• rs200894397
• NM_001143975.1:c.460C>T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001143975.1(UBTFL1):​c.460C>T​(p.Arg154Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000281 in 1,528,156 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R154Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00019 (4 hom., cov: 23)
  • Exomes 𝑓: 0.00029 (50 hom.)
• Consequence: UBTFL1 NM_001143975.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.661

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

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.063256145).
• BS2: High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBTFL1	NM_001143975.1	c.460C>T	p.Arg154Trp	missense_variant	Exon 1 of 1	ENST00000530464.2	NP_001137447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBTFL1	ENST00000530464.2	c.460C>T	p.Arg154Trp	missense_variant	Exon 1 of 1	6	NM_001143975.1	ENSP00000485108.1

Frequencies

GnomAD3 genomes AF: 0.000188 AC: 26 AN: 138208 Hom.: 4 Cov.: 23

Gnomad AFR AF: 0.0000260

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000473

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000342

Gnomad OTH AF: 0.000531

GnomAD3 exomes AF: 0.000354 AC: 78 AN: 220180 Hom.: 9 AF XY: 0.000272 AC XY: 33 AN XY: 121172

Gnomad AFR exome AF: 0.0000704

Gnomad AMR exome AF: 0.000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000347

Gnomad FIN exome AF: 0.0000531

Gnomad NFE exome AF: 0.000569

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000290 AC: 403 AN: 1389858 Hom.: 50 Cov.: 31 AF XY: 0.000264 AC XY: 183 AN XY: 692072

Gnomad4 AFR exome AF: 0.0000921

Gnomad4 AMR exome AF: 0.000249

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000109

Gnomad4 FIN exome AF: 0.0000630

Gnomad4 NFE exome AF: 0.000343

Gnomad4 OTH exome AF: 0.000207

GnomAD4 genome AF: 0.000188 AC: 26 AN: 138298 Hom.: 4 Cov.: 23 AF XY: 0.000240 AC XY: 16 AN XY: 66630

Gnomad4 AFR AF: 0.0000259

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000473

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000342

Gnomad4 OTH AF: 0.000525

Alfa AF: 0.000401 Hom.: 1

ExAC AF: 0.000285 AC: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.460C>T (p.R154W) alteration is located in exon 1 (coding exon 1) of the UBTFL1 gene. This alteration results from a C to T substitution at nucleotide position 460, causing the arginine (R) at amino acid position 154 to be replaced by a tryptophan (W). 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	Benign	0.095
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Benign	0.90
DEOGEN2	Uncertain	0.68	D
FATHMM_MKL	Benign	0.033	N
LIST_S2	Uncertain	0.95	D
MetaRNN	Benign	0.063	T
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.56	T
Sift4G	Uncertain	0.0080	D
Polyphen		0.99	D
Vest4		0.17
MVP		0.22
GERP RS		0.085
Varity_R		0.20
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

Publications

LitVar

Other links and lift over

dbSNP: rs200894397; hg19: chr11-89819577; COSMIC: COSV73297789;