Genetic Variant UBTFL1:p.Asp209Gly (chr11-90086575-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001143975.1(UBTFL1):c.626A>G(p.Asp209Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000076 ( 0 hom., cov: 22)

Exomes 𝑓: 0.0000024 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UBTFL1
NM_001143975.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.11

Publications

0 publications found

Variant links:

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]

UBTFL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.059776574).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBTFL1	NM_001143975.1 link	c.626A>G	p.Asp209Gly	missense_variant	Exon 1 of 1	ENST00000530464.2	NP_001137447.1	P0CB47

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBTFL1	ENST00000530464.2 link	c.626A>G	p.Asp209Gly	missense_variant	Exon 1 of 1	6	NM_001143975.1	ENSP00000485108.1		P0CB47

Frequencies

GnomAD3 genomes

AF:

0.00000760

AC:

AN:

131610

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000273

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000992

AC:

AN:

100818

AF XY:

0.0000185

show subpopulations

Gnomad AFR exome

AF:

0.000142

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000241

AC:

AN:

1242524

Hom.:

Cov.:

AF XY:

0.00000160

AC XY:

AN XY:

625976

show subpopulations

African (AFR)

AF:

0.000102

AC:

AN:

29398

American (AMR)

AF:

0.00

AC:

AN:

32246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24640

East Asian (EAS)

AF:

0.00

AC:

AN:

34744

South Asian (SAS)

AF:

0.00

AC:

AN:

77876

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47256

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3752

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

939670

Other (OTH)

AF:

0.00

AC:

AN:

52942

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000760

AC:

AN:

131610

Hom.:

Cov.:

AF XY:

0.0000158

AC XY:

AN XY:

63170

show subpopulations

African (AFR)

AF:

0.0000273

AC:

AN:

36654

American (AMR)

AF:

0.00

AC:

AN:

11262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3236

East Asian (EAS)

AF:

0.00

AC:

AN:

3924

South Asian (SAS)

AF:

0.00

AC:

AN:

3720

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8196

Middle Eastern (MID)

AF:

0.00

AC:

AN:

296

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

61758

Other (OTH)

AF:

0.00

AC:

AN:

1736

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 09, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.626A>G (p.D209G) alteration is located in exon 1 (coding exon 1) of the UBTFL1 gene. This alteration results from a A to G substitution at nucleotide position 626, causing the aspartic acid (D) at amino acid position 209 to be replaced by a glycine (G). 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

0.089

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.43

CADD

Benign

1.2

(source)

DANN

Benign

0.32

DEOGEN2

Benign

0.026

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.29

MetaRNN

Benign

0.060

MutationAssessor

Benign

1.6

PhyloP100

-1.1

PrimateAI

Benign

0.47

Sift4G

Benign

0.37

Polyphen

0.0060

Vest4

0.086

MVP

0.081

GERP RS

-2.1

Varity_R

0.11

gMVP

0.099

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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11-90086575-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over