9-65283173-C-T

Variant names:

• chr9-65283173-C-T
• NM_001126334.1:c.1205G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001126334.1(FOXD4L5):​c.1205G>A​(p.Arg402Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 10)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXD4L5 NM_001126334.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.16

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06857368).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXD4L5	NM_001126334.1	c.1205G>A	p.Arg402Lys	missense_variant	Exon 1 of 1	ENST00000377420.1	NP_001119806.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXD4L5	ENST00000377420.1	c.1205G>A	p.Arg402Lys	missense_variant	Exon 1 of 1	6	NM_001126334.1	ENSP00000366637.1

Frequencies

GnomAD3 genomes Cov.: 10

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.60e-7 AC: 1 AN: 1163410 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 579076

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000113

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 10

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1205G>A (p.R402K) alteration is located in exon 1 (coding exon 1) of the FOXD4L5 gene. This alteration results from a G to A substitution at nucleotide position 1205, causing the arginine (R) at amino acid position 402 to be replaced by a lysine (K). 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	0.14
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	7.1
DANN	Benign	0.94
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00062	N
LIST_S2	Benign	0.31	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.069	T
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Benign	0.69	N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.13	T
Polyphen		0.0	B
Vest4		0.086
MutPred		0.26		Gain of relative solvent accessibility (P = 0.0479);
MVP		0.048
ClinPred		0.077	T
GERP RS		-0.38
Varity_R		0.11
gMVP		0.019

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-70176779;