19-19218926-A-G

Variant names:

• chr19-19218926-A-G
• NM_004386.3:c.85A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004386.3(NCAN):​c.85A>G​(p.Ile29Val) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NCAN NM_004386.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.558
• Publications: 0 publications found

Genes affected

NCAN (HGNC:2465): (neurocan) Neurocan is a chondroitin sulfate proteoglycan thought to be involved in the modulation of cell adhesion and migration.[supplied by OMIM, Jul 2002]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05682406).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004386.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAN	NM_004386.3	MANE Select	c.85A>G	p.Ile29Val	missense	Exon 3 of 15	NP_004377.2	O14594

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAN	ENST00000252575.11	TSL:1 MANE Select	c.85A>G	p.Ile29Val	missense	Exon 3 of 15	ENSP00000252575.4	O14594
	NCAN	ENST00000910091.1		c.85A>G	p.Ile29Val	missense	Exon 4 of 16	ENSP00000580150.1
	NCAN	ENST00000952495.1		c.85A>G	p.Ile29Val	missense	Exon 3 of 15	ENSP00000622554.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1364466 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 668002

African (AFR) AF: 0.00 AC: 0 AN: 30456

American (AMR) AF: 0.00 AC: 0 AN: 31042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20250

East Asian (EAS) AF: 0.00 AC: 0 AN: 38236

South Asian (SAS) AF: 0.00 AC: 0 AN: 70522

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5322

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1062898

Other (OTH) AF: 0.00 AC: 0 AN: 56180

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	0.10
DANN	Benign	0.22
DEOGEN2	Benign	0.083	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.56
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.18
Sift	Benign	0.54	T
Sift4G	Benign	0.40	T
Polyphen		0.0070	B
Vest4		0.022
MutPred		0.50		Loss of sheet (P = 0.0817)
MVP		0.36
MPC		0.33
ClinPred		0.018	T
GERP RS		-4.3
Varity_R		0.019
gMVP		0.30
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

hg19: chr19-19329735;