11-68684970-C-T

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.47C>T(p.Ala16Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00922 in 1,608,498 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0078 (13 hom., cov: 33)
  • Exomes 𝑓: 0.0094 (99 hom.)
• Consequence: GAL NM_015973.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0120

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=0.0037229955).
• BP6: Variant 11-68684970-C-T is Benign according to our data. Variant chr11-68684970-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 475915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 1188 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAL	NM_015973.5	c.47C>T	p.Ala16Val	missense_variant	2/6	ENST00000265643.4
LOC107984343	XR_001748281.1	n.230+2871G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAL	ENST00000265643.4	c.47C>T	p.Ala16Val	missense_variant	2/6	1	NM_015973.5	P1

Frequencies

GnomAD3 genomes AF: 0.00780 AC: 1188 AN: 152222 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.00217

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.00549

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00696

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.00812

GnomAD3 exomes AF: 0.00681 AC: 1586 AN: 232814 Hom.: 7 AF XY: 0.00667 AC XY: 850 AN XY: 127484

Gnomad AFR exome AF: 0.00209

Gnomad AMR exome AF: 0.00354

Gnomad ASJ exome AF: 0.0174

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000745

Gnomad FIN exome AF: 0.00821

Gnomad NFE exome AF: 0.0101

Gnomad OTH exome AF: 0.00821

GnomAD4 exome AF: 0.00937 AC: 13650 AN: 1456160 Hom.: 99 Cov.: 29 AF XY: 0.00925 AC XY: 6697 AN XY: 724198

Gnomad4 AFR exome AF: 0.00177

Gnomad4 AMR exome AF: 0.00383

Gnomad4 ASJ exome AF: 0.0178

Gnomad4 EAS exome AF: 0.0000505

Gnomad4 SAS exome AF: 0.000820

Gnomad4 FIN exome AF: 0.00901

Gnomad4 NFE exome AF: 0.0107

Gnomad4 OTH exome AF: 0.00841

GnomAD4 genome AF: 0.00779 AC: 1187 AN: 152338 Hom.: 13 Cov.: 33 AF XY: 0.00714 AC XY: 532 AN XY: 74498

Gnomad4 AFR AF: 0.00216

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00696

Gnomad4 NFE AF: 0.0117

Gnomad4 OTH AF: 0.00803

Alfa AF: 0.0112 Hom.: 5

Bravo AF: 0.00760

TwinsUK AF: 0.00998 AC: 37

ALSPAC AF: 0.0106 AC: 41

ESP6500AA AF: 0.00297 AC: 13

ESP6500EA AF: 0.00982 AC: 84

ExAC AF: 0.00641 AC: 773

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/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

Mar 21, 2019

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	10
Dann	Benign	0.96
DEOGEN2	Benign	0.27	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.022
Sift	Benign	0.074	T
Sift4G	Benign	0.21	T
Polyphen		0.0040	B
Vest4		0.29
MVP		0.27
MPC		0.12
ClinPred		0.0035	T
GERP RS		-0.28
Varity_R		0.051
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34725707; hg19: chr11-68452438; COSMIC: COSV105046679; COSMIC: COSV105046679;