1-47438328-G-C

Variant names:

• chr1-47438328-G-C
• rs78469326
• NM_004474.4:c.193G>C

Variant summary

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

The NM_004474.4(FOXD2):​c.193G>C​(p.Ala65Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000175 in 1,141,462 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A65T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: FOXD2 NM_004474.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 0 publications found

Genes affected

FOXD2 (HGNC:3803): (forkhead box D2) This gene belongs to the forkhead family of transcription factors which is characterized by a distinct forkhead domain. The specific function of this gene has not yet been determined. [provided by RefSeq, Jul 2008]

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=0.18812153).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXD2	NM_004474.4	c.193G>C	p.Ala65Pro	missense_variant	Exon 1 of 1	ENST00000334793.6	NP_004465.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXD2	ENST00000334793.6	c.193G>C	p.Ala65Pro	missense_variant	Exon 1 of 1	6	NM_004474.4	ENSP00000335493.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000175 AC: 2 AN: 1141462 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 548324

African (AFR) AF: 0.00 AC: 0 AN: 23178

American (AMR) AF: 0.00 AC: 0 AN: 8716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15364

East Asian (EAS) AF: 0.00 AC: 0 AN: 26690

South Asian (SAS) AF: 0.00 AC: 0 AN: 39808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26996

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3432

European-Non Finnish (NFE) AF: 0.00000210 AC: 2 AN: 951490

Other (OTH) AF: 0.00 AC: 0 AN: 45788

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Benign	0.90
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.48	T
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.2
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.14
Sift	Uncertain	0.025	D
Sift4G	Benign	0.28	T
Polyphen		0.072	B
Vest4		0.10
MutPred		0.27		Gain of loop (P = 0.002);
MVP		0.55
ClinPred		0.090	T
GERP RS		4.1
PromoterAI		0.024	Neutral
Varity_R		0.16
gMVP		0.18
Mutation Taster		=78/22	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: rs78469326; hg19: chr1-47904000;