chr17-63917314-AGCCACAGCT-A

Position:

• chr17-63917314-AGCCACAGCT-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_000515.5(GH1):​c.640_648delAGCTGTGGC​(p.Ser214_Gly216del) variant causes a conservative inframe deletion change. 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: GH1 NM_000515.5 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.09

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]

ENSG00000285947 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000515.5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GH1	NM_000515.5	c.640_648delAGCTGTGGC	p.Ser214_Gly216del	conservative_inframe_deletion	5/5	ENST00000323322.10	NP_000506.2
GH1	NM_022559.4	c.595_603delAGCTGTGGC	p.Ser199_Gly201del	conservative_inframe_deletion	5/5		NP_072053.1
GH1	NM_022560.4	c.520_528delAGCTGTGGC	p.Ser174_Gly176del	conservative_inframe_deletion	4/4		NP_072054.1
LOC112268204	XR_002958148.2	n.341-279_341-271delACAGCTGCC		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GH1	ENST00000323322.10	c.640_648delAGCTGTGGC	p.Ser214_Gly216del	conservative_inframe_deletion	5/5	1	NM_000515.5	ENSP00000312673.5
ENSG00000285947	ENST00000647774.1	c.916_924delAGCTGTGGC	p.Ser306_Gly308del	conservative_inframe_deletion	8/8			ENSP00000497443.1

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal dominant isolated somatotropin deficiency Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

MVZ Medizinische Genetik Mainz

Jul 22, 2024

ACMG Criteria: PM4,PM2_SUP,PP1,PP3 -

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr17-61994674;