17-35121880-G-C

Variant names:

• chr17-35121880-G-C
• rs759420533
• NM_017559.4:c.187G>C

Variant summary

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

The NM_017559.4(FNDC8):​c.187G>C​(p.Glu63Gln) 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. 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. E63K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 27)
• Consequence: FNDC8 NM_017559.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228

Genes affected

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

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=0.065065205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNDC8	NM_017559.4	c.187G>C	p.Glu63Gln	missense_variant	Exon 1 of 4	ENST00000158009.6	NP_060029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FNDC8	ENST00000158009.6	c.187G>C	p.Glu63Gln	missense_variant	Exon 1 of 4	1	NM_017559.4	ENSP00000158009.4

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.23
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.019
Sift	Benign	0.16	T
Sift4G	Benign	0.16	T
Polyphen		0.079	B
Vest4		0.12
MutPred		0.11		Gain of catalytic residue at E63 (P = 0.1131);
MVP		0.36
MPC		0.12
ClinPred		0.079	T
GERP RS		1.6
PromoterAI		-0.0073	Neutral
Varity_R		0.070
gMVP		0.26

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

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Other links and lift over

dbSNP: rs759420533; hg19: chr17-33448899;