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GeneBe

17-63917490-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000515.5(GH1):c.473G>T(p.Ser158Ile) variant causes a missense 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. 9/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S158S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

GH1
NM_000515.5 missense

Scores

1
2
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17986876).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GH1NM_000515.5 linkuse as main transcriptc.473G>T p.Ser158Ile missense_variant 5/5 ENST00000323322.10
LOC112268204XR_002958148.2 linkuse as main transcriptn.341-107C>A intron_variant, non_coding_transcript_variant
GH1NM_022559.4 linkuse as main transcriptc.428G>T p.Ser143Ile missense_variant 5/5
GH1NM_022560.4 linkuse as main transcriptc.353G>T p.Ser118Ile missense_variant 4/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GH1ENST00000323322.10 linkuse as main transcriptc.473G>T p.Ser158Ile missense_variant 5/51 NM_000515.5 P1P01241-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxSep 14, 2022Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.095
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Uncertain
-0.020
Cadd
Benign
19
Dann
Benign
0.94
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.37
FATHMM_MKL
Benign
0.59
D
M_CAP
Uncertain
0.13
D
MetaRNN
Benign
0.18
T
MutationTaster
Benign
1.0
D;D;D;D;D
Sift4G
Pathogenic
0.0
D
Polyphen
0.0040
B
Vest4
0.19
MVP
0.56
ClinPred
0.92
D
GERP RS
0.25

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: chr17-61994850; API