6-159214983-C-G

Variant names:

• chr6-159214983-C-G
• rs762962324
• NM_032532.3:c.499C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032532.3(FNDC1):​c.499C>G​(p.Arg167Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R167Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FNDC1 NM_032532.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.65
• Publications: 1 publications found

Genes affected

FNDC1 (HGNC:21184): (fibronectin type III domain containing 1) Predicted to act upstream of or within several processes, including cellular response to hypoxia; positive regulation of cardiac muscle cell apoptotic process; and positive regulation of protein phosphorylation. Located in nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032532.3. 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
	FNDC1	NM_032532.3	MANE Select	c.499C>G	p.Arg167Gly	missense	Exon 5 of 23	NP_115921.2	Q4ZHG4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNDC1	ENST00000297267.14	TSL:1 MANE Select	c.499C>G	p.Arg167Gly	missense	Exon 5 of 23	ENSP00000297267.9	Q4ZHG4-1
	FNDC1	ENST00000329629.8	TSL:1	c.373C>G	p.Arg125Gly	missense	Exon 4 of 21	ENSP00000333297.8	J3KNQ2
	FNDC1	ENST00000906655.1		c.148C>G	p.Arg50Gly	missense	Exon 2 of 20	ENSP00000576714.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461676 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727116

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111862

Other (OTH) AF: 0.00 AC: 0 AN: 60366

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	Uncertain	0.38
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0073	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.90	L
PhyloP100		3.7
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.28
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.55
MutPred		0.57		Loss of MoRF binding (P = 0.0202)
MVP		0.80
MPC		0.21
ClinPred		0.94	D
GERP RS		6.2
Varity_R		0.28
gMVP		0.67
Mutation Taster		=75/25	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: rs762962324; hg19: chr6-159636015;