rs950065093

Variant names:

• chr20-44257282-C-G
• rs950065093
• NM_024034.6:c.310C>G

Your query was ambiguous. Multiple possible variants found:

• chr20-44257282-C-G
• chr20-44257282-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024034.6(GDAP1L1):​c.310C>G​(p.Arg104Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GDAP1L1 NM_024034.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.58

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08013484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDAP1L1	NM_024034.6	c.310C>G	p.Arg104Gly	missense_variant	Exon 2 of 6	ENST00000342560.10	NP_076939.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDAP1L1	ENST00000342560.10	c.310C>G	p.Arg104Gly	missense_variant	Exon 2 of 6	1	NM_024034.6	ENSP00000341782.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Benign	0.61
DEOGEN2	Benign	0.0037	T;T;.;.;.;.
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.72	T;T;T;T;T;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.080	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.0	.;N;N;.;.;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	3.7	.;N;.;.;N;N
REVEL	Benign	0.11
Sift	Benign	1.0	.;T;.;.;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T
Polyphen		0.0010	.;B;.;.;.;.
Vest4		0.34
MutPred		0.54		.;Loss of stability (P = 0.0848);Loss of stability (P = 0.0848);Loss of stability (P = 0.0848);Loss of stability (P = 0.0848);Loss of stability (P = 0.0848);
MVP		0.35
MPC		0.61
ClinPred		0.18	T
GERP RS		3.5
Varity_R		0.093
gMVP		0.23

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

LitVar

Other links and lift over

dbSNP: rs950065093; hg19: chr20-42885922;