3-47569114-G-T

Variant names:

• chr3-47569114-G-T
• rs1440439692
• ENST00000383738.6:c.1496C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001206943.2(CSPG5):​c.1496C>A​(p.Pro499His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000278 in 1,439,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P499L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: CSPG5 NM_001206943.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.35
• Publications: 0 publications found

Genes affected

CSPG5 (HGNC:2467): (chondroitin sulfate proteoglycan 5) The protein encoded by this gene is a proteoglycan that may function as a neural growth and differentiation factor. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3627972).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206943.2. 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
	CSPG5	NM_006574.4	MANE Select	c.1458+38C>A		intron	N/A	NP_006565.2	O95196-2
	CSPG5	NM_001206943.2		c.1496C>A	p.Pro499His	missense	Exon 4 of 5	NP_001193872.1	O95196-1
	CSPG5	NM_001206945.2		c.1082C>A	p.Pro361His	missense	Exon 4 of 5	NP_001193874.1	B7Z2E0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSPG5	ENST00000383738.6	TSL:1	c.1496C>A	p.Pro499His	missense	Exon 4 of 5	ENSP00000373244.2	O95196-1
	CSPG5	ENST00000264723.9	TSL:1 MANE Select	c.1458+38C>A		intron	N/A	ENSP00000264723.4	O95196-2
	CSPG5	ENST00000456150.5	TSL:1	c.1044+38C>A		intron	N/A	ENSP00000392096.1	O95196-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000278 AC: 4 AN: 1439182 Hom.: 0 Cov.: 31 AF XY: 0.00000420 AC XY: 3 AN XY: 715054

African (AFR) AF: 0.00 AC: 0 AN: 32088

American (AMR) AF: 0.00 AC: 0 AN: 41056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24734

East Asian (EAS) AF: 0.00 AC: 0 AN: 38420

South Asian (SAS) AF: 0.0000484 AC: 4 AN: 82702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52748

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5644

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102366

Other (OTH) AF: 0.00 AC: 0 AN: 59424

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.032
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.4
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.21
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.17	B
Vest4		0.52
MutPred		0.59		Gain of sheet (P = 0.0221)
MVP		0.30
MPC		1.6
ClinPred		0.86	D
GERP RS		4.7
Varity_R		0.28
gMVP		0.35
Mutation Taster		=72/28	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

dbSNP: rs1440439692; hg19: chr3-47610604;