rs201458814

Variant names:

• chr6-159200052-C-A
• rs201458814
• NM_032532.3:c.361C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-159200052-C-A
• chr6-159200052-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032532.3(FNDC1):​c.361C>A​(p.Arg121Ser) 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 pathogenic 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. R121C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FNDC1 NM_032532.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.812

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNDC1	NM_032532.3	c.361C>A	p.Arg121Ser	missense_variant	Exon 3 of 23	ENST00000297267.14	NP_115921.2
FNDC1	XM_011536190.3	c.361C>A	p.Arg121Ser	missense_variant	Exon 3 of 22		XP_011534492.1
FNDC1	XM_011536191.3	c.110-14893C>A		intron_variant	Intron 1 of 19		XP_011534493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FNDC1	ENST00000297267.14	c.361C>A	p.Arg121Ser	missense_variant	Exon 3 of 23	1	NM_032532.3	ENSP00000297267.9
FNDC1	ENST00000329629.8	c.235C>A	p.Arg79Ser	missense_variant	Exon 2 of 21	1		ENSP00000333297.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1451426 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 720610

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0099	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.010	T
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.55	N
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.22
Sift	Benign	0.040	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.46		Gain of glycosylation at R121 (P = 0.007);
MVP		0.75
MPC		0.18
ClinPred		0.98	D
GERP RS		6.0
Varity_R		0.26
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.20		Position offset: 30

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201458814; hg19: chr6-159621084;