3-47576888-A-G

Variant names:

• chr3-47576888-A-G
• NM_006574.4:c.1138T>C

Variant summary

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

The NM_006574.4(CSPG5):​c.1138T>C​(p.Tyr380His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSPG5 NM_006574.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.00

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSPG5	NM_006574.4	c.1138T>C	p.Tyr380His	missense_variant	Exon 2 of 5	ENST00000264723.9	NP_006565.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSPG5	ENST00000264723.9	c.1138T>C	p.Tyr380His	missense_variant	Exon 2 of 5	1	NM_006574.4	ENSP00000264723.4
CSPG5	ENST00000383738.6	c.1138T>C	p.Tyr380His	missense_variant	Exon 2 of 5	1		ENSP00000373244.2
CSPG5	ENST00000456150.5	c.724T>C	p.Tyr242His	missense_variant	Exon 1 of 4	1		ENSP00000392096.1
CSPG5	ENST00000610462.1	c.1138T>C	p.Tyr380His	missense_variant	Exon 2 of 4	5		ENSP00000478923.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1138T>C (p.Y380H) alteration is located in exon 2 (coding exon 2) of the CSPG5 gene. This alteration results from a T to C substitution at nucleotide position 1138, causing the tyrosine (Y) at amino acid position 380 to be replaced by a histidine (H). 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	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	.;D;.;T
Eigen	Benign	0.090
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.43	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	.;L;L;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-4.1	D;D;D;.
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D;D;D;.
Sift4G	Benign	0.065	T;T;T;T
Polyphen		0.035, 0.060	.;B;B;.
Vest4		0.74
MutPred		0.55		.;Gain of disorder (P = 0.1623);Gain of disorder (P = 0.1623);Gain of disorder (P = 0.1623);
MVP		0.23
MPC		1.7
ClinPred		1.0	D
GERP RS		4.6
Varity_R		0.77
gMVP		0.93

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: chr3-47618378; COSMIC: COSV53130089; COSMIC: COSV53130089;