chr9-65283137-C-G

Variant names:

• chr9-65283137-C-G
• rs1417991035
• NM_001126334.1:c.1241G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001126334.1(FOXD4L5):​c.1241G>C​(p.Arg414Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/21 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. R414G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00055 (1 hom., cov: 9)
  • Exomes 𝑓: 0.00031 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXD4L5 NM_001126334.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.86
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013286352).

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.1241G>C	p.Arg414Pro	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.1241G>C	p.Arg414Pro	missense	Exon 1 of 1	ENSP00000366637.1	Q5VV16

Frequencies

GnomAD3 genomes AF: 0.000546 AC: 28 AN: 51274 Hom.: 1 Cov.: 9

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000420

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0149

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000847

Gnomad OTH AF: 0.00156

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000307 AC: 276 AN: 899946 Hom.: 0 Cov.: 12 AF XY: 0.000300 AC XY: 136 AN XY: 453056

African (AFR) AF: 0.00 AC: 0 AN: 23578

American (AMR) AF: 0.00 AC: 0 AN: 31692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18862

East Asian (EAS) AF: 0.00765 AC: 239 AN: 31224

South Asian (SAS) AF: 0.00 AC: 0 AN: 61854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31984

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2988

European-Non Finnish (NFE) AF: 0.0000335 AC: 22 AN: 656708

Other (OTH) AF: 0.000365 AC: 15 AN: 41056

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000546 AC: 28 AN: 51320 Hom.: 1 Cov.: 9 AF XY: 0.000560 AC XY: 13 AN XY: 23202

African (AFR) AF: 0.00 AC: 0 AN: 15082

American (AMR) AF: 0.000419 AC: 2 AN: 4774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1378

East Asian (EAS) AF: 0.0150 AC: 23 AN: 1532

South Asian (SAS) AF: 0.00 AC: 0 AN: 1192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 184

European-Non Finnish (NFE) AF: 0.0000848 AC: 2 AN: 23596

Other (OTH) AF: 0.00153 AC: 1 AN: 654

Alfa AF: 0.0000843 Hom.: 0

Bravo AF: 0.000302

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	0.10
BayesDel_addAF	Benign	-0.0038	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	9.7
DANN	Uncertain	0.98
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.33	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.013	T
MetaSVM	Uncertain	-0.011	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.9
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	0.010	N
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.84	P
Vest4		0.16
MutPred		0.17		Gain of glycosylation at R414 (P = 0.0029)
MVP		0.16
ClinPred		0.40	T
Varity_R		0.13
gMVP		0.028
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: rs1417991035; hg19: chr9-70176743; COSMIC: COSV66240476; COSMIC: COSV66240476;