9-65283212-C-A

Variant names:

• chr9-65283212-C-A
• rs1823512273
• NM_001126334.1:c.1166G>T

Variant summary

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

The NM_001126334.1(FOXD4L5):​c.1166G>T​(p.Ser389Ile) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S389R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 11)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXD4L5 NM_001126334.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.375
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18054059).

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.1166G>T	p.Ser389Ile	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.1166G>T	p.Ser389Ile	missense	Exon 1 of 1	ENSP00000366637.1	Q5VV16

Frequencies

GnomAD3 genomes Cov.: 11

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1329000 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 663148

African (AFR) AF: 0.00 AC: 0 AN: 30050

American (AMR) AF: 0.00 AC: 0 AN: 40086

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24792

East Asian (EAS) AF: 0.00 AC: 0 AN: 34088

South Asian (SAS) AF: 0.00 AC: 0 AN: 81182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3880

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1012248

Other (OTH) AF: 0.00 AC: 0 AN: 55068

GnomAD4 genome Cov.: 11

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.24	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.18	T
MetaSVM	Uncertain	-0.090	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.38
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.030	D
Polyphen		0.97	D
Vest4		0.35
MutPred		0.27		Gain of sheet (P = 0.0266)
MVP		0.33
ClinPred		0.27	T
Varity_R		0.062
gMVP		0.038
Mutation Taster		=97/3	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: rs1823512273; hg19: chr9-70176818;