19-39203911-C-G

Position:

• chr19-39203911-C-G

Variant summary

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

The NM_001080468.4(SYCN):​c.344G>C​(p.Arg115Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SYCN NM_001080468.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.830

Genes affected

SYCN (HGNC:18442): (syncollin) Predicted to be involved in exocytosis. Predicted to be active in secretory granule membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.41749257).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYCN	NM_001080468.4	c.344G>C	p.Arg115Pro	missense_variant	1/2	ENST00000318438.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYCN	ENST00000318438.7	c.344G>C	p.Arg115Pro	missense_variant	1/2	1	NM_001080468.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459310 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725772

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T
Eigen	Benign	0.044
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	0.90	N
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.17
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.40
MutPred		0.35		Loss of helix (P = 0.0237);
MVP		0.41
MPC		0.79
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.84
gMVP		0.86

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: chr19-39694551;