16-31182415-A-T

Variant names:

• chr16-31182415-A-T
• rs750230722
• NM_004960.4:c.31A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004960.4(FUS):​c.31A>T​(p.Thr11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FUS NM_004960.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.42

Genes affected

FUS (HGNC:4010): (FUS RNA binding protein) This gene encodes a multifunctional protein component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complex. The hnRNP complex is involved in pre-mRNA splicing and the export of fully processed mRNA to the cytoplasm. This protein belongs to the FET family of RNA-binding proteins which have been implicated in cellular processes that include regulation of gene expression, maintenance of genomic integrity and mRNA/microRNA processing. Alternative splicing results in multiple transcript variants. Defects in this gene result in amyotrophic lateral sclerosis type 6. [provided by RefSeq, Sep 2009]

ENSG00000260304 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17832533).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUS	NM_004960.4	c.31A>T	p.Thr11Ser	missense_variant	Exon 2 of 15	ENST00000254108.12	NP_004951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUS	ENST00000254108.12	c.31A>T	p.Thr11Ser	missense_variant	Exon 2 of 15	1	NM_004960.4	ENSP00000254108.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Benign	0.92
DEOGEN2	Benign	0.23	T;.;T
Eigen	Benign	-0.22
Eigen_PC	Benign	0.017
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.49	T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.80	N;N;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	0.18	N;N;N
REVEL	Benign	0.24
Sift	Benign	0.68	T;T;T
Sift4G	Benign	0.79	T;T;T
Polyphen		0.010	B;B;.
Vest4		0.34
MutPred		0.21		Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);
MVP		0.69
MPC		0.18
ClinPred		0.45	T
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.090
gMVP		0.29

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: rs750230722; hg19: chr16-31193736;