NM_004474.4:c.160C>T

Variant names:

• chr1-47438295-C-T
• rs1246268188
• NM_004474.4:c.160C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_004474.4(FOXD2):​c.160C>T​(p.His54Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000936 in 1,174,664 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. H54D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000094 (0 hom.)
• Consequence: FOXD2 NM_004474.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.411
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.102357835).
• BS2: High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXD2	NM_004474.4	c.160C>T	p.His54Tyr	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.160C>T	p.His54Tyr	missense_variant	Exon 1 of 1	6	NM_004474.4	ENSP00000335493.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 3996 AF XY: 0.00

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 AF: 0.00000936 AC: 11 AN: 1174664 Hom.: 0 Cov.: 30 AF XY: 0.0000106 AC XY: 6 AN XY: 568546

African (AFR) AF: 0.00 AC: 0 AN: 23722

American (AMR) AF: 0.00 AC: 0 AN: 9934

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16252

East Asian (EAS) AF: 0.00 AC: 0 AN: 26988

South Asian (SAS) AF: 0.00 AC: 0 AN: 46578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3628

European-Non Finnish (NFE) AF: 0.0000113 AC: 11 AN: 971916

Other (OTH) AF: 0.00 AC: 0 AN: 47336

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.045	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.50	T
M_CAP	Pathogenic	0.96	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	-0.69	N
PhyloP100		0.41
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.18
Sift	Benign	0.084	T
Sift4G	Benign	0.94	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.23		Gain of phosphorylation at H54 (P = 0.0092);
MVP		0.19
ClinPred		0.098	T
GERP RS		-1.6
PromoterAI		-0.016	Neutral
Varity_R		0.061
gMVP		0.21
Mutation Taster		=92/8	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: rs1246268188; hg19: chr1-47903967;