NM_021081.6:c.106A>G

Variant names:

• chr20-37256476-T-C
• rs28932185
• NM_021081.6:c.106A>G

Variant summary

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

The NM_021081.6(GHRH):​c.106A>G​(p.Ile36Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,908 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: 6.8e-7 (0 hom.)
• Consequence: GHRH NM_021081.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.14

Genes affected

GHRH (HGNC:4265): (growth hormone releasing hormone) This gene encodes a member of the glucagon family of proteins. The encoded preproprotein is produced in the hypothalamus and cleaved to generate the mature factor, known as somatoliberin, which acts to stimulate growth hormone release from the pituitary gland. Variant receptors for somatoliberin have been found in several types of tumors, and antagonists of these receptors can inhibit the growth of the tumors. Defects in this gene are a cause of dwarfism, while hypersecretion of the encoded protein is a cause of gigantism. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

ACMG classification

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
GHRH	NM_021081.6	c.106A>G	p.Ile36Val	missense_variant	Exon 3 of 5	ENST00000373614.7	NP_066567.1
GHRH	NM_001184731.3	c.106A>G	p.Ile36Val	missense_variant	Exon 3 of 5		NP_001171660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHRH	ENST00000373614.7	c.106A>G	p.Ile36Val	missense_variant	Exon 3 of 5	1	NM_021081.6	ENSP00000362716.2
GHRH	ENST00000237527.8	c.106A>G	p.Ile36Val	missense_variant	Exon 3 of 5	1		ENSP00000237527.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460908 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726712

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000316 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T;T;.
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.86	.;D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;M;M
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.70	N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0090	D;D;D
Sift4G	Uncertain	0.025	D;D;T
Polyphen		0.98	D;D;P
Vest4		0.56
MutPred		0.52		Gain of phosphorylation at Y32 (P = 0.1181);Gain of phosphorylation at Y32 (P = 0.1181);Gain of phosphorylation at Y32 (P = 0.1181);
MVP		0.47
MPC		0.84
ClinPred		0.84	D
GERP RS		3.9
Varity_R		0.28
gMVP		0.52

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

LitVar

Other links and lift over

dbSNP: rs28932185; hg19: chr20-35884879;