20-31844921-C-A

Variant names:

• chr20-31844921-C-A
• rs201517755
• NM_004118.4:c.622G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004118.4(FOXS1):​c.622G>T​(p.Val208Leu) 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. 17/22 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. V208M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FOXS1 NM_004118.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 0 publications found

Genes affected

FOXS1 (HGNC:3735): (forkhead box S1) The forkhead family of transcription factors belongs to the winged helix class of DNA-binding proteins. The protein encoded by this intronless gene contains a forkhead domain and is found predominantly in aorta and kidney. The function of the encoded protein is unknown. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060035586).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004118.4. 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
	FOXS1	NM_004118.4	MANE Select	c.622G>T	p.Val208Leu	missense	Exon 1 of 1	NP_004109.1	O43638

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXS1	ENST00000375978.5	TSL:6 MANE Select	c.622G>T	p.Val208Leu	missense	Exon 1 of 1	ENSP00000365145.3	O43638

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	1.3
DANN	Benign	0.70
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	1.3	L
PhyloP100		-1.2
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.13
Sift	Benign	0.46	T
Sift4G	Benign	0.69	T
Polyphen		0.0010	B
Vest4		0.056
MutPred		0.16		Gain of glycosylation at P207 (P = 0.1098)
MVP		0.71
MPC		0.18
ClinPred		0.026	T
GERP RS		1.3
Varity_R		0.034
gMVP		0.14
Mutation Taster		=96/4	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: rs201517755; hg19: chr20-30432724;