rs1557115507

Variant names:

• chrX-49251353-T-C
• rs1557115507
• NM_014009.4:c.1277A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_014009.4(FOXP3):​c.1277A>G​(p.Asn426Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,291 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: FOXP3 NM_014009.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0250

Genes affected

FOXP3 (HGNC:6106): (forkhead box P3) The protein encoded by this gene is a member of the forkhead/winged-helix family of transcriptional regulators. Defects in this gene are the cause of immunodeficiency polyendocrinopathy, enteropathy, X-linked syndrome (IPEX), also known as X-linked autoimmunity-immunodeficiency syndrome. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11958358).
• BP6: Variant X-49251353-T-C is Benign according to our data. Variant chrX-49251353-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1947433.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP3	NM_014009.4	c.1277A>G	p.Asn426Ser	missense_variant	Exon 12 of 12	ENST00000376207.10	NP_054728.2
FOXP3	NM_001114377.2	c.1172A>G	p.Asn391Ser	missense_variant	Exon 11 of 11		NP_001107849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP3	ENST00000376207.10	c.1277A>G	p.Asn426Ser	missense_variant	Exon 12 of 12	1	NM_014009.4	ENSP00000365380.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.00000566 AC: 1 AN: 176693 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 62003

Gnomad AFR exome AF: 0.0000791

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 9.12e-7 AC: 1 AN: 1096291 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 361863

Gnomad4 AFR exome AF: 0.0000379

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Insulin-dependent diabetes mellitus secretory diarrhea syndrome Benign:1

May 28, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;.;T;.;.;.
FATHMM_MKL	Benign	0.58	D
LIST_S2	Uncertain	0.88	D;D;D;T;.;T
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.12	T;T;T;T;T;T
MetaSVM	Uncertain	0.098	D
MutationAssessor	Benign	0.81	L;.;.;.;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.29	N;N;.;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.032	D;D;.;D;D;D
Sift4G	Benign	0.74	T;T;T;T;T;T
Polyphen		0.080	B;B;B;B;B;.
Vest4		0.10
MutPred		0.26		Gain of phosphorylation at N426 (P = 0.0021);.;.;.;.;.;
MVP		0.85
MPC		0.41
ClinPred		0.059	T
GERP RS		3.2
Varity_R		0.078
gMVP		0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs1557115507; hg19: chrX-49107814;