3-172448354-G-C

Variant names:

• chr3-172448354-G-C
• NM_198407.2:c.60C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198407.2(GHSR):​c.60C>G​(p.Asp20Glu) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D20D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GHSR NM_198407.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300

Genes affected

GHSR (HGNC:4267): (growth hormone secretagogue receptor) This gene encodes a member of the G-protein coupled receptor family. The encoded protein may play a role in energy homeostasis and regulation of body weight. Two identified transcript variants are expressed in several tissues and are evolutionary conserved in fish and swine. One transcript, 1a, excises an intron and encodes the functional protein; this protein is the receptor for the Ghrelin ligand and defines a neuroendocrine pathway for growth hormone release. The second transcript (1b) retains the intron and does not function as a receptor for Ghrelin; however, it may function to attenuate activity of isoform 1a. Mutations in this gene are associated with autosomal idiopathic short stature.[provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06772846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GHSR	NM_198407.2	c.60C>G	p.Asp20Glu	missense_variant	Exon 1 of 2	ENST00000241256.3	NP_940799.1
GHSR	NM_004122.2	c.60C>G	p.Asp20Glu	missense_variant	Exon 1 of 1		NP_004113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHSR	ENST00000241256.3	c.60C>G	p.Asp20Glu	missense_variant	Exon 1 of 2	1	NM_198407.2	ENSP00000241256.2
GHSR	ENST00000427970.1	c.60C>G	p.Asp20Glu	missense_variant	Exon 1 of 1	6		ENSP00000395344.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	2.6
DANN	Benign	0.54
DEOGEN2	Benign	0.11	T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.42	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.068	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.030	N;N
REVEL	Benign	0.020
Sift	Benign	0.62	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.018	B;B
Vest4		0.032
MutPred		0.34		Gain of phosphorylation at S24 (P = 0.2046);Gain of phosphorylation at S24 (P = 0.2046);
MVP		0.53
MPC		0.85
ClinPred		0.076	T
GERP RS		0.052
Varity_R		0.050
gMVP		0.40

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: chr3-172166144;