NM_001448.3:c.1623C>G

Variant names:

• chrX-133302915-G-C
• rs2068272893
• NM_001448.3:c.1623C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001448.3(GPC4):​c.1623C>G​(p.Leu541Leu) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: GPC4 NM_001448.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.59
• Publications: 0 publications found

Genes affected

GPC4 (HGNC:4452): (glypican 4) Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with a variable number of heparan sulfate chains. Members of the glypican-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a glycosyl phosphatidylinositol linkage. These proteins may play a role in the control of cell division and growth regulation. The GPC4 gene is adjacent to the 3' end of GPC3 and may also play a role in Simpson-Golabi-Behmel syndrome. [provided by RefSeq, Jul 2008]

GPC4 Gene-Disease associations (from GenCC):

• Keipert syndrome

  Inheritance: XLR, XL Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant X-133302915-G-C is Benign according to our data. Variant chrX-133302915-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2661465.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.59 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001448.3. 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
	GPC4	NM_001448.3	MANE Select	c.1623C>G	p.Leu541Leu	synonymous	Exon 9 of 9	NP_001439.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC4	ENST00000370828.4	TSL:1 MANE Select	c.1623C>G	p.Leu541Leu	synonymous	Exon 9 of 9	ENSP00000359864.3	O75487-1
	GPC4	ENST00000887818.1		c.1623C>G	p.Leu541Leu	synonymous	Exon 10 of 10	ENSP00000557877.1
	GPC4	ENST00000931828.1		c.1623C>G	p.Leu541Leu	synonymous	Exon 10 of 10	ENSP00000601887.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.6
DANN	Benign	0.66
PhyloP100		1.6

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: rs2068272893; hg19: chrX-132436943;