NM_018972.4:c.1045T>G

Variant names:

• chr8-74364335-T-G
• NM_018972.4:c.1045T>G

Variant summary

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

The NM_018972.4(GDAP1):​c.1045T>G​(p.Leu349Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GDAP1 NM_018972.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.838

Genes affected

GDAP1 (HGNC:15968): (ganglioside induced differentiation associated protein 1) This gene encodes a member of the ganglioside-induced differentiation-associated protein family, which may play a role in a signal transduction pathway during neuronal development. Mutations in this gene have been associated with various forms of Charcot-Marie-Tooth Disease and neuropathy. Two transcript variants encoding different isoforms and a noncoding variant have been identified 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=0.13214567).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDAP1	NM_018972.4	c.1045T>G	p.Leu349Val	missense_variant	Exon 6 of 6	ENST00000220822.12	NP_061845.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDAP1	ENST00000220822.12	c.1045T>G	p.Leu349Val	missense_variant	Exon 6 of 6	1	NM_018972.4	ENSP00000220822.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461778 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727198

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

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	0.060
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T;.
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.51
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Uncertain	0.38	D
MutationAssessor	Benign	0.69	N;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.040	N;N
REVEL	Benign	0.28
Sift	Uncertain	0.014	D;D
Sift4G	Uncertain	0.036	D;D
Polyphen		0.10	B;.
Vest4		0.34
MutPred		0.25		Gain of sheet (P = 0.0149);.;
MVP		0.84
MPC		0.46
ClinPred		0.066	T
GERP RS		2.5
Varity_R		0.044
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-75276570;