rs782669868

Variant names:

• chr17-81528543-C-A
• rs782669868
• NM_012418.4:c.12C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-81528543-C-A
• chr17-81528543-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012418.4(FSCN2):​c.12C>A​(p.Asn4Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FSCN2 NM_012418.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

Genes affected

FSCN2 (HGNC:3960): (fascin actin-bundling protein 2, retinal) This gene encodes a member of the fascin protein family. Fascins crosslink actin into filamentous bundles within dynamic cell extensions. This family member is proposed to play a role in photoreceptor disk morphogenesis. A mutation in this gene results in one form of autosomal dominant retinitis pigmentosa and macular degeneration. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31747383).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSCN2	NM_012418.4	c.12C>A	p.Asn4Lys	missense_variant	Exon 1 of 5	ENST00000417245.7	NP_036550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSCN2	ENST00000417245.7	c.12C>A	p.Asn4Lys	missense_variant	Exon 1 of 5	1	NM_012418.4	ENSP00000388716.2
FSCN2	ENST00000334850.7	c.12C>A	p.Asn4Lys	missense_variant	Exon 1 of 5	5		ENSP00000334665.7

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000445 AC: 1 AN: 224590 Hom.: 0 AF XY: 0.00000816 AC XY: 1 AN XY: 122600

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000308

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443568 Hom.: 0 Cov.: 32 AF XY: 0.00000140 AC XY: 1 AN XY: 716068

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000233

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.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.4
DANN	Benign	0.92
DEOGEN2	Benign	0.22	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.77	T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.25
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.97	D;.
Vest4		0.64
MutPred		0.32		Gain of methylation at N4 (P = 0.0094);Gain of methylation at N4 (P = 0.0094);
MVP		0.20
MPC		0.42
ClinPred		0.75	D
GERP RS		-10
Varity_R		0.54
gMVP		0.61

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

LitVar

Other links and lift over

dbSNP: rs782669868; hg19: chr17-79495569;