rs763293774

Variant names:

• chr17-35127335-C-A
• rs763293774
• NM_017559.4:c.503C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-35127335-C-A
• chr17-35127335-C-T

Variant summary

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

The NM_017559.4(FNDC8):​c.503C>A​(p.Thr168Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. T168M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FNDC8 NM_017559.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

Genes affected

FNDC8 (HGNC:25286): (fibronectin type III domain containing 8) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.20358306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNDC8	NM_017559.4	c.503C>A	p.Thr168Lys	missense_variant	Exon 2 of 4	ENST00000158009.6	NP_060029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FNDC8	ENST00000158009.6	c.503C>A	p.Thr168Lys	missense_variant	Exon 2 of 4	1	NM_017559.4	ENSP00000158009.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458382 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725528

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.016
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.0	M
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.21		Gain of ubiquitination at T168 (P = 0.0022);
MVP		0.18
MPC		0.58
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.76
gMVP		0.36

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: rs763293774; hg19: chr17-33454354;