17-63917907-GCG-ACC

Variant names:

• chr17-63917907-GCG-ACC
• NM_000515.5:c.307_309delCGCinsGGT
• GH1 p.Arg103Gly

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM5

The NM_000515.5(GH1):​c.307_309delCGCinsGGT​(p.Arg103Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. R103C) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GH1 NM_000515.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.75
• Publications: 0 publications found

Genes affected

GH1 (HGNC:4261): (growth hormone 1) The protein encoded by this gene is a member of the somatotropin/prolactin family of hormones which play an important role in growth control. The gene, along with four other related genes, is located at the growth hormone locus on chromosome 17 where they are interspersed in the same transcriptional orientation; an arrangement which is thought to have evolved by a series of gene duplications. The five genes share a remarkably high degree of sequence identity. Alternative splicing generates additional isoforms of each of the five growth hormones, leading to further diversity and potential for specialization. This particular family member is expressed in the pituitary but not in placental tissue as is the case for the other four genes in the growth hormone locus. Mutations in or deletions of the gene lead to growth hormone deficiency and short stature. [provided by RefSeq, Jul 2008]

GH1 Gene-Disease associations (from GenCC):

• isolated growth hormone deficiency type IA

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• isolated growth hormone deficiency type II

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• isolated growth hormone deficiency type IB

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• short stature due to growth hormone qualitative anomaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285947 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM5: Other missense variant is known to change same aminoacid residue: Variant chr17-63917909-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 15969.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000515.5. 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
	GH1	NM_000515.5	MANE Select	c.307_309delCGCinsGGT	p.Arg103Gly	missense	N/A	NP_000506.2
	GH1	NM_022559.4		c.262_264delCGCinsGGT	p.Arg88Gly	missense	N/A	NP_072053.1	B1A4G7
	GH1	NM_022560.4		c.187_189delCGCinsGGT	p.Arg63Gly	missense	N/A	NP_072054.1	P01241-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GH1	ENST00000323322.10	TSL:1 MANE Select	c.307_309delCGCinsGGT	p.Arg103Gly	missense	N/A	ENSP00000312673.5	P01241-1
	ENSG00000285947	ENST00000647774.1		c.583_585delCGCinsGGT	p.Arg195Gly	missense	N/A	ENSP00000497443.1	A0A3B3ISS9
	GH1	ENST00000458650.6	TSL:1	c.262_264delCGCinsGGT	p.Arg88Gly	missense	N/A	ENSP00000408486.2	P01241-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-61995267;