dbSNP rs200409102: GH1:p.Gly187Arg (chr17-63917404-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_000515.5(GH1):c.559G>C(p.Gly187Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,680 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GH1
NM_000515.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.70

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]

GH1 links:

ENSG00000285947 (HGNC:):

ENSG00000285947 links:

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ACMG classification

Classification made for transcript

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
GH1	NM_000515.5 link	c.559G>C	p.Gly187Arg	missense_variant	Exon 5 of 5	ENST00000323322.10	NP_000506.2	P01241-1B1A4G6
GH1	NM_022559.4 link	c.514G>C	p.Gly172Arg	missense_variant	Exon 5 of 5		NP_072053.1	P01241-2B1A4G7
GH1	NM_022560.4 link	c.439G>C	p.Gly147Arg	missense_variant	Exon 4 of 4		NP_072054.1	P01241-5
LOC112268204	XR_002958148.2 link	n.341-193C>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GH1	ENST00000323322.10 link	c.559G>C	p.Gly187Arg	missense_variant	Exon 5 of 5	1	NM_000515.5	ENSP00000312673.5		P01241-1
ENSG00000285947	ENST00000647774.1 link	c.835G>C	p.Gly279Arg	missense_variant	Exon 8 of 8			ENSP00000497443.1		A0A3B3ISS9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461680

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Pathogenic

0.81

.;.;D;D

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.87

D;D;D;D

M_CAP

Uncertain

0.099

MetaRNN

Uncertain

0.73

D;D;D;D

MetaSVM

Benign

-0.56

MutationAssessor

Benign

0.94

.;.;L;.

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-4.3

D;D;D;D

REVEL

Uncertain

0.55

Sift

Benign

0.075

T;T;T;T

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.11, 0.0030

.;.;B;B

Vest4

0.69

MutPred

0.64

.;.;Gain of MoRF binding (P = 0.0309);.;

MVP

0.91

MPC

0.13

ClinPred

0.70

GERP RS

2.6

Varity_R

0.70

gMVP

0.50

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over