rs1372740408

Variant names:

• chr1-47438259-C-A
• rs1372740408
• NM_004474.4:c.124C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-47438259-C-A
• chr1-47438259-C-T

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.124C>A​(p.Arg42Ser) 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. 14/22 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. R42H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXD2 NM_004474.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.473
• 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=0.1625315).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXD2	NM_004474.4	c.124C>A	p.Arg42Ser	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.124C>A	p.Arg42Ser	missense_variant	Exon 1 of 1	6	NM_004474.4	ENSP00000335493.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000800 AC: 1 AN: 12502 AF XY: 0.000133

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1216962 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 593442

African (AFR) AF: 0.00 AC: 0 AN: 24296

American (AMR) AF: 0.00 AC: 0 AN: 12114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17936

East Asian (EAS) AF: 0.00 AC: 0 AN: 27338

South Asian (SAS) AF: 0.00 AC: 0 AN: 55088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29446

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3666

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 997506

Other (OTH) AF: 0.00 AC: 0 AN: 49572

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.54	T
M_CAP	Pathogenic	0.99	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.47
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	0.21	N
REVEL	Benign	0.19
Sift	Benign	0.13	T
Sift4G	Benign	0.72	T
Polyphen		0.0030	B
Vest4		0.16
MutPred		0.28		Gain of glycosylation at R42 (P = 0.0118);
MVP		0.74
ClinPred		0.056	T
GERP RS		1.5
PromoterAI		0.0059	Neutral
Varity_R		0.12
gMVP		0.28
Mutation Taster		=93/7	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: rs1372740408; hg19: chr1-47903931;