Variant rs137853220 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_000515.5(GH1):c.307C>T(p.Arg103Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

GH1
NM_000515.5 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.75

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:

LOC112268204 (HGNC:):

LOC112268204 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.965

PP5

Variant 17-63917909-G-A is Pathogenic according to our data. Variant chr17-63917909-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 15969.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GH1	NM_000515.5 linkuse as main transcript	c.307C>T	p.Arg103Cys	missense_variant	4/5	ENST00000323322.10	NP_000506.2
LOC112268204	XR_002958148.2 linkuse as main transcript	n.508G>A		non_coding_transcript_exon_variant	3/3
GH1	NM_022559.4 linkuse as main transcript	c.262C>T	p.Arg88Cys	missense_variant	4/5		NP_072053.1
GH1	NM_022560.4 linkuse as main transcript	c.187C>T	p.Arg63Cys	missense_variant	3/4		NP_072054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GH1	ENST00000323322.10 linkuse as main transcript	c.307C>T	p.Arg103Cys	missense_variant	4/5	1	NM_000515.5	ENSP00000312673	P1	P01241-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251426

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727240

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Short stature due to growth hormone qualitative anomaly

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 01, 2007

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.91

.;.;D

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.81

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Uncertain

0.20

MetaRNN

Pathogenic

0.97

D;D;D

MetaSVM

Uncertain

0.46

MutationAssessor

Uncertain

2.5

.;.;M

MutationTaster

Benign

1.0

A;A;A;A;A

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-5.6

D;D;D

REVEL

Pathogenic

0.69

Sift

Uncertain

0.010

D;D;D

Sift4G

Uncertain

0.023

D;D;D

Polyphen

0.085

.;.;B

Vest4

0.63

MutPred

0.87

.;.;Gain of catalytic residue at S105 (P = 0.0188);

MVP

0.93

MPC

0.15

ClinPred

0.96

GERP RS

1.8

Varity_R

0.57

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over