chr9-65283485-C-G

Variant names:

• chr9-65283485-C-G
• rs1226043421
• NM_001126334.1:c.893G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001126334.1(FOXD4L5):​c.893G>C​(p.Cys298Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C298Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 22)
• Consequence: FOXD4L5 NM_001126334.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.83
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07633716).

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.893G>C	p.Cys298Ser	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.893G>C	p.Cys298Ser	missense	Exon 1 of 1	ENSP00000366637.1	Q5VV16

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	0.061
DANN	Benign	0.41
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.32	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.0	N
PhyloP100		-5.8
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.21
Sift	Uncertain	0.026	D
Sift4G	Benign	0.79	T
Polyphen		0.0030	B
Vest4		0.038
MutPred		0.52		Loss of catalytic residue at P297 (P = 0.0066)
MVP		0.088
ClinPred		0.11	T
GERP RS		-2.1
Varity_R		0.10
gMVP		0.039
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1226043421; hg19: chr9-70177091;