Genetic Variant GAL:p.Glu121Lys (chr11-68690976-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015973.5(GAL):c.361G>A(p.Glu121Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000678 in 1,610,068 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00038 ( 3 hom. )

Consequence

GAL
NM_015973.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.06

Publications

3 publications found

Variant links:

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]

GAL Gene-Disease associations (from GenCC):

familial temporal lobe epilepsy 8
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

GAL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031820834).

BP6

Variant 11-68690976-G-A is Benign according to our data. Variant chr11-68690976-G-A is described in ClinVar as Benign. ClinVar VariationId is 475913.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 531 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015973.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAL	NM_015973.5	MANE Select	c.361G>A	p.Glu121Lys	missense	Exon 6 of 6	NP_057057.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GAL	ENST00000265643.4	TSL:1 MANE Select	c.361G>A	p.Glu121Lys	missense	Exon 6 of 6	ENSP00000265643.3	P22466
GAL	ENST00000933457.1		c.559G>A	p.Glu187Lys	missense	Exon 7 of 7	ENSP00000603516.1
GAL	ENST00000933456.1		c.415G>A	p.Glu139Lys	missense	Exon 6 of 6	ENSP00000603515.1

Frequencies

GnomAD3 genomes

AF:

0.00348

AC:

529

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000959

GnomAD2 exomes

AF:

0.000991

AC:

249

AN:

251252

AF XY:

0.000758

show subpopulations

Gnomad AFR exome

AF:

0.0138

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000385

AC:

561

AN:

1457854

Hom.:

Cov.:

AF XY:

0.000340

AC XY:

247

AN XY:

725506

show subpopulations

African (AFR)

AF:

0.0140

AC:

466

AN:

33388

American (AMR)

AF:

0.000693

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86178

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53152

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

1108586

Other (OTH)

AF:

0.000713

AC:

AN:

60278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.430

Heterozygous variant carriers

117

146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00349

AC:

531

AN:

152214

Hom.:

Cov.:

AF XY:

0.00333

AC XY:

248

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0125

AC:

518

AN:

41520

American (AMR)

AF:

0.000589

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000208

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68026

Other (OTH)

AF:

0.000949

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

108

135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000380

Hom.:

Bravo

AF:

0.00410

ESP6500AA

AF:

0.0102

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00116

AC:

141

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial temporal lobe epilepsy 8 (1)

GAL-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0032

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

1.1

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.43

REVEL

Benign

0.054

Sift

Benign

0.076

Sift4G

Benign

0.22

Polyphen

0.42

Vest4

0.17

MVP

0.49

MPC

0.51

ClinPred

0.0086

GERP RS

1.9

Varity_R

0.066

gMVP

0.12

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over