Genetic Variant FOXD4L5:p.Thr393Pro (chr9-65283201-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001126334.1(FOXD4L5):c.1177A>C(p.Thr393Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 11)

Exomes 𝑓: 0.000014 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

FOXD4L5
NM_001126334.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0670

Publications

0 publications found

Variant links:

Genes affected

FOXD4L5 (HGNC:18522): (forkhead box D4 like 5) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in anatomical structure morphogenesis; cell differentiation; and regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

FOXD4L5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12794724).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001126334.1. 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
	FOXD4L5	NM_001126334.1	MANE Select	c.1177A>C	p.Thr393Pro	missense	Exon 1 of 1	NP_001119806.1	Q5VV16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXD4L5	ENST00000377420.1	TSL:6 MANE Select	c.1177A>C	p.Thr393Pro	missense	Exon 1 of 1	ENSP00000366637.1	Q5VV16

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

88946

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000141

AC:

AN:

1277340

Hom.:

Cov.:

AF XY:

0.00000942

AC XY:

AN XY:

636880

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29004

American (AMR)

AF:

0.00

AC:

AN:

37608

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23986

East Asian (EAS)

AF:

0.000514

AC:

AN:

33060

South Asian (SAS)

AF:

0.00

AC:

AN:

78430

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44268

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3796

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

973788

Other (OTH)

AF:

0.0000187

AC:

AN:

53400

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

89046

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

41298

African (AFR)

AF:

0.00

AC:

AN:

23494

American (AMR)

AF:

0.00

AC:

AN:

8030

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2368

East Asian (EAS)

AF:

0.00

AC:

AN:

2042

South Asian (SAS)

AF:

0.00

AC:

AN:

1922

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4888

Middle Eastern (MID)

AF:

0.00

AC:

AN:

230

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

44390

Other (OTH)

AF:

0.00

AC:

AN:

1050

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000491

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.015

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.18

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.13

MetaSVM

Uncertain

-0.086

MutationAssessor

Benign

-0.34

PhyloP100

0.067

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.34

REVEL

Benign

0.27

Sift

Pathogenic

0.0

Sift4G

Benign

0.21

Polyphen

0.82

Vest4

0.16

MutPred

0.18

Loss of phosphorylation at T393 (P = 0.0147)

MVP

0.067

ClinPred

0.17

Varity_R

0.13

gMVP

0.026

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over