dbSNP rs375779631: GDAP1L1:p.Ala36Thr (chr20-44247440-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024034.6(GDAP1L1):c.106G>A(p.Ala36Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000479 in 1,608,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

GDAP1L1
NM_024034.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.07

Publications

0 publications found

Variant links:

Genes affected

GDAP1L1 (HGNC:4213): (ganglioside induced differentiation associated protein 1 like 1) The ganglioside GD3 synthase causes cell differentiation with neurite sprouting when transfected into the mouse neuroblastoma cell line Neuro2a. After differentiation, the expression of several genes is upregulated, including one that encodes a protein termed ganglioside-induced differentiation-associated protein 1 (Gdap1). A similar gene was found in humans, and mutations in the human gene are associated with Charcot-Marie-Tooth type 4A disease. The protein encoded by this gene is similar in sequence to the human GDAP1 protein. Several transcript variants encoding different isoforms, as well as a noncoding transcript variant, have been found for this gene. [provided by RefSeq, Feb 2012]

GDAP1L1 links:

ENSG00000304405 (HGNC:):

ENSG00000304405 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09040874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDAP1L1	NM_024034.6 link	c.106G>A	p.Ala36Thr	missense_variant	Exon 1 of 6	ENST00000342560.10	NP_076939.3	Q96MZ0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDAP1L1	ENST00000342560.10 link	c.106G>A	p.Ala36Thr	missense_variant	Exon 1 of 6	1	NM_024034.6	ENSP00000341782.5		Q96MZ0-1

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000506

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000302

AC:

AN:

231870

AF XY:

0.0000157

show subpopulations

Gnomad AFR exome

AF:

0.000295

Gnomad AMR exome

AF:

0.0000594

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:

0.000178

GnomAD4 exome

AF:

0.0000330

AC:

AN:

1455928

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

723924

show subpopulations

African (AFR)

AF:

0.000750

AC:

AN:

33312

American (AMR)

AF:

0.000113

AC:

AN:

44290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25978

East Asian (EAS)

AF:

0.00

AC:

AN:

39362

South Asian (SAS)

AF:

0.00

AC:

AN:

85408

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51792

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00000721

AC:

AN:

1110012

Other (OTH)

AF:

0.000167

AC:

AN:

60018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000190

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.000505

AC:

AN:

41584

American (AMR)

AF:

0.000392

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68034

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

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:

0.0000564

Hom.:

Bravo

AF:

0.000223

ESP6500AA

AF:

0.000460

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000249

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 17, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.106G>A (p.A36T) alteration is located in exon 1 (coding exon 1) of the GDAP1L1 gene. This alteration results from a G to A substitution at nucleotide position 106, causing the alanine (A) at amino acid position 36 to be replaced by a threonine (T). 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

0.066

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.010

T;.;.;.;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.73

T;T;T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.090

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;.;.;N

PhyloP100

2.1

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.39

N;.;.;N;N

REVEL

Benign

0.20

Sift

Benign

0.50

T;.;.;T;T

Sift4G

Benign

0.58

T;T;T;T;T

Polyphen

0.0

B;.;.;.;.

Vest4

0.091

MVP

0.92

MPC

0.48

ClinPred

0.034

GERP RS

2.2

PromoterAI

0.041

Neutral

(source)

Varity_R

0.051

gMVP

0.27

Mutation Taster

=78/22

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over