19-56177133-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033106.4(GALP):c.25G>C(p.Val9Leu) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GALP NM_033106.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0670

Genes affected

GALP (HGNC:24840): (galanin like peptide) This gene encodes a member of the galanin family of neuropeptides. The encoded protein binds galanin receptors 1, 2 and 3 with the highest affinity for galanin receptor 3 and has been implicated in biological processes involving the central nervous system including hypothalamic regulation of metabolism and reproduction. A peptide encoded by a splice variant of this gene, termed alarin, has vasoactive properties, displays antimicrobial activity against E. coli, and may serve as a marker for neuroblastic tumors.[provided by RefSeq, Nov 2014]

ACMG classification

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=0.07169333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALP	NM_033106.4	c.25G>C	p.Val9Leu	missense_variant	2/6	ENST00000357330.7
GALP	NM_001145546.2	c.25G>C	p.Val9Leu	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALP	ENST00000357330.7	c.25G>C	p.Val9Leu	missense_variant	2/6	1	NM_033106.4	P2
GALP	ENST00000590002.1	c.25G>C	p.Val9Leu	missense_variant	1/2	1		A2
GALP	ENST00000440823.1	c.25G>C	p.Val9Leu	missense_variant	2/5	5		A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 28, 2023

The c.25G>C (p.V9L) alteration is located in exon 2 (coding exon 1) of the GALP gene. This alteration results from a G to C substitution at nucleotide position 25, causing the valine (V) at amino acid position 9 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	2.2
Dann	Benign	0.53
DEOGEN2	Benign	0.077	T;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.32	T;T;.
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.072	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.050	N;D;.
REVEL	Benign	0.015
Sift	Benign	0.055	T;.;.
Sift4G	Benign	0.30	T;D;D
Polyphen		0.0030	B;B;B
Vest4		0.21
MutPred		0.35		Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);
MVP		0.067
MPC		0.099
ClinPred		0.060	T
GERP RS		1.3
Varity_R		0.082
gMVP		0.053

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: chr19-56688502;