20-44258478-G-C

Variant names:

• chr20-44258478-G-C
• NM_024034.6:c.418G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024034.6(GDAP1L1):​c.418G>C​(p.Ala140Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,400,180 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: GDAP1L1 NM_024034.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.44

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDAP1L1	NM_024034.6	c.418G>C	p.Ala140Pro	missense_variant	Exon 3 of 6	ENST00000342560.10	NP_076939.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDAP1L1	ENST00000342560.10	c.418G>C	p.Ala140Pro	missense_variant	Exon 3 of 6	1	NM_024034.6	ENSP00000341782.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1400180 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 691626

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T;T;.;.
Eigen	Benign	0.095
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.81	T;T;T;T
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.45	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	.;N;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.26	.;N;.;.
REVEL	Uncertain	0.64
Sift	Benign	0.52	.;T;.;.
Sift4G	Benign	0.62	T;T;T;T
Polyphen		0.17	.;B;.;.
Vest4		0.65
MutPred		0.51		.;Loss of helix (P = 0.0041);.;Loss of helix (P = 0.0041);
MVP		0.95
MPC		0.62
ClinPred		0.33	T
GERP RS		5.3
Varity_R		0.22
gMVP		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-42887118;