9-65283300-G-C

Variant names:

• chr9-65283300-G-C
• rs1823513299
• NM_001126334.1:c.1078C>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001126334.1(FOXD4L5):​c.1078C>G​(p.Gln360Glu) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000048 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXD4L5 NM_001126334.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.76

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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06622028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXD4L5	NM_001126334.1	c.1078C>G	p.Gln360Glu	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.1078C>G	p.Gln360Glu	missense_variant	Exon 1 of 1	6	NM_001126334.1	ENSP00000366637.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000480 AC: 7 AN: 1457550 Hom.: 0 Cov.: 35 AF XY: 0.00000828 AC XY: 6 AN XY: 724764

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: 0.00000631

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1078C>G (p.Q360E) alteration is located in exon 1 (coding exon 1) of the FOXD4L5 gene. This alteration results from a C to G substitution at nucleotide position 1078, causing the glutamine (Q) at amino acid position 360 to be replaced by a glutamic acid (E). 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	0.070
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.33	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.18
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.23	T
Polyphen		0.032	B
Vest4		0.071
MutPred		0.28		Gain of solvent accessibility (P = 0.0145);
MVP		0.061
ClinPred		0.13	T
GERP RS		1.1
Varity_R		0.11
gMVP		0.018

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: rs1823513299; hg19: chr9-70176906;