chr6-159215095-A-G

Position:

• chr6-159215095-A-G

Variant summary

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

The NM_032532.3(FNDC1):​c.611A>G​(p.Lys204Arg) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FNDC1 NM_032532.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.89

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2146123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FNDC1	NM_032532.3	c.611A>G	p.Lys204Arg	missense_variant	5/23	ENST00000297267.14
FNDC1	XM_011536190.3	c.542A>G	p.Lys181Arg	missense_variant	4/22
FNDC1	XM_011536191.3	c.260A>G	p.Lys87Arg	missense_variant	2/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FNDC1	ENST00000297267.14	c.611A>G	p.Lys204Arg	missense_variant	5/23	1	NM_032532.3	P1
FNDC1	ENST00000329629.8	c.488A>G	p.Lys163Arg	missense_variant	4/21	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.611A>G (p.K204R) alteration is located in exon 5 (coding exon 5) of the FNDC1 gene. This alteration results from a A to G substitution at nucleotide position 611, causing the lysine (K) at amino acid position 204 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Benign	0.92
DEOGEN2	Benign	0.0063	T
Eigen	Benign	0.039
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.32	N
MutationTaster	Benign	0.68	N;N
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.16
Sift	Benign	0.10	T
Sift4G	Benign	0.49	T
Polyphen		0.89	P
Vest4		0.20
MutPred		0.53		Loss of ubiquitination at K204 (P = 0.0134);
MVP		0.73
MPC		0.13
ClinPred		0.83	D
GERP RS		5.0
Varity_R		0.091
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-159636127; COSMIC: COSV51948320; COSMIC: COSV51948320;