rs145825008

chr11-68688878-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_015973.5(GAL):c.253A>G(p.Asn85Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,574,282 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (7 hom.)
• Consequence: GAL NM_015973.5 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.347

Genes affected

GAL (HGNC:4114): (galanin and GMAP prepropeptide) This gene encodes a neuroendocrine peptide that is widely expressed in the central and peripheral nervous systems and also the gastrointestinal tract, pancreas, adrenal gland and urogenital tract. The encoded protein is a precursor that is proteolytically processed to generate two mature peptides: galanin and galanin message-associated peptide (GMAP). Galanin has diverse physiological functions including nociception, feeding and energy homeostasis, osmotic regulation and water balance. GMAP has been demonstrated to possess antifungal activity and hypothesized to be part of the innate immune system. [provided by RefSeq, Jul 2015]

LOC107984343 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007835507).
• BP6: Variant 11-68688878-A-G is Benign according to our data. Variant chr11-68688878-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 542527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 194 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAL	NM_015973.5	c.253A>G	p.Asn85Asp	missense_variant	5/6	ENST00000265643.4
LOC107984343	XR_001748281.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAL	ENST00000265643.4	c.253A>G	p.Asn85Asp	missense_variant	5/6	1	NM_015973.5	P1

Frequencies

GnomAD3 genomes AF: 0.00127 AC: 194 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000506

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00240

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00148 AC: 372 AN: 251210 Hom.: 1 AF XY: 0.00149 AC XY: 202 AN XY: 135814

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.000795

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.00288

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.00216 AC: 3067 AN: 1421942 Hom.: 7 Cov.: 25 AF XY: 0.00214 AC XY: 1516 AN XY: 710068

Gnomad4 AFR exome AF: 0.000489

Gnomad4 AMR exome AF: 0.000246

Gnomad4 ASJ exome AF: 0.000657

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000222

Gnomad4 FIN exome AF: 0.000337

Gnomad4 NFE exome AF: 0.00268

Gnomad4 OTH exome AF: 0.00158

GnomAD4 genome AF: 0.00127 AC: 193 AN: 152340 Hom.: 0 Cov.: 32 AF XY: 0.000980 AC XY: 73 AN XY: 74496

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.00240

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00214 Hom.: 1

Bravo AF: 0.00128

TwinsUK AF: 0.00351 AC: 13

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00268 AC: 23

ExAC AF: 0.00175 AC: 213

EpiCase AF: 0.00300

EpiControl AF: 0.00373

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

GAL-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 04, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Familial temporal lobe epilepsy 8 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

May 15, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.75
Cadd	Benign	3.6
Dann	Benign	0.64
DEOGEN2	Benign	0.32	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.0078	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.088
Sift	Benign	0.36	T
Sift4G	Benign	0.42	T
Polyphen		0.0020	B
Vest4		0.13
MVP		0.34
MPC		0.14
ClinPred		0.0033	T
GERP RS		0.036
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs145825008; hg19: chr11-68456346;