chr19-56182251-C-G

Position:

• chr19-56182251-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033106.4(GALP):​c.216C>G​(p.Ile72Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 1,608,358 control chromosomes in the GnomAD database, including 100,043 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.34 (9111 hom., cov: 31)
  • Exomes 𝑓: 0.35 (90932 hom.)
• Consequence: GALP NM_033106.4 missense, splice_region
• Scores: Splicing: ADA: 0.0007041
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005278021).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALP	NM_033106.4	c.216C>G	p.Ile72Met	missense_variant, splice_region_variant	4/6	ENST00000357330.7
GALP	NM_001145546.2	c.*17C>G		splice_region_variant, 3_prime_UTR_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALP	ENST00000357330.7	c.216C>G	p.Ile72Met	missense_variant, splice_region_variant	4/6	1	NM_033106.4	P2
GALP	ENST00000440823.1	c.*17C>G		splice_region_variant, 3_prime_UTR_variant	3/5	5		A2
GALP	ENST00000590002.1			downstream_gene_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52124 AN: 151838 Hom.: 9108 Cov.: 31

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.358

GnomAD3 exomes AF: 0.338 AC: 84876 AN: 250948 Hom.: 14609 AF XY: 0.342 AC XY: 46346 AN XY: 135624

Gnomad AFR exome AF: 0.341

Gnomad AMR exome AF: 0.327

Gnomad ASJ exome AF: 0.313

Gnomad EAS exome AF: 0.218

Gnomad SAS exome AF: 0.355

Gnomad FIN exome AF: 0.315

Gnomad NFE exome AF: 0.363

Gnomad OTH exome AF: 0.341

GnomAD4 exome AF: 0.351 AC: 511175 AN: 1456402 Hom.: 90932 Cov.: 30 AF XY: 0.351 AC XY: 254677 AN XY: 724878

Gnomad4 AFR exome AF: 0.336

Gnomad4 AMR exome AF: 0.326

Gnomad4 ASJ exome AF: 0.305

Gnomad4 EAS exome AF: 0.219

Gnomad4 SAS exome AF: 0.361

Gnomad4 FIN exome AF: 0.323

Gnomad4 NFE exome AF: 0.360

Gnomad4 OTH exome AF: 0.340

GnomAD4 genome AF: 0.343 AC: 52165 AN: 151956 Hom.: 9111 Cov.: 31 AF XY: 0.341 AC XY: 25309 AN XY: 74262

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.360

Alfa AF: 0.331 Hom.: 5252

Bravo AF: 0.345

TwinsUK AF: 0.350 AC: 1297

ALSPAC AF: 0.371 AC: 1430

ESP6500AA AF: 0.340 AC: 1496

ESP6500EA AF: 0.362 AC: 3109

ExAC AF: 0.343 AC: 41683

EpiCase AF: 0.367

EpiControl AF: 0.360

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.2
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.0053	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
MutationTaster	Benign	0.96	P;P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.91	P
Vest4		0.054
MPC		0.20
ClinPred		0.041	T
GERP RS		-2.4
Varity_R		0.19
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00070
dbscSNV1_RF	Benign	0.028
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

Other links and lift over

dbSNP: rs3745833; hg19: chr19-56693620; COSMIC: COSV61999231; COSMIC: COSV61999231;