chr6-159200076-C-T

Position:

• chr6-159200076-C-T

Variant summary

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

The NM_032532.3(FNDC1):​c.385C>T​(p.Pro129Ser) 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. 16/21 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: 2.45

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=0.15002128).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FNDC1	NM_032532.3	c.385C>T	p.Pro129Ser	missense_variant	3/23	ENST00000297267.14
FNDC1	XM_011536190.3	c.385C>T	p.Pro129Ser	missense_variant	3/22
FNDC1	XM_011536191.3	c.110-14869C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FNDC1	ENST00000297267.14	c.385C>T	p.Pro129Ser	missense_variant	3/23	1	NM_032532.3	P1
FNDC1	ENST00000329629.8	c.262C>T	p.Pro88Ser	missense_variant	2/21	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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

Oct 05, 2023

The c.385C>T (p.P129S) alteration is located in exon 3 (coding exon 3) of the FNDC1 gene. This alteration results from a C to T substitution at nucleotide position 385, causing the proline (P) at amino acid position 129 to be replaced by a serine (S). 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	0.17
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.096
Sift	Benign	0.52	T
Sift4G	Benign	0.10	T
Polyphen		0.65	P
Vest4		0.37
MutPred		0.33		Loss of catalytic residue at P129 (P = 0.016);
MVP		0.72
MPC		0.16
ClinPred		0.32	T
GERP RS		5.1
Varity_R		0.11
gMVP		0.40

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: chr6-159621108;