NM_024034.6:c.199G>T

Variant names:

• chr20-44257171-G-T
• rs1000998948
• NM_024034.6:c.199G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024034.6(GDAP1L1):​c.199G>T​(p.Glu67*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GDAP1L1 NM_024034.6 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.64
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024034.6. 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
	GDAP1L1	NM_024034.6	MANE Select	c.199G>T	p.Glu67*	stop_gained	Exon 2 of 6	NP_076939.3
	GDAP1L1	NM_001256737.2		c.199G>T	p.Glu67*	stop_gained	Exon 2 of 6	NP_001243666.1	Q96MZ0-4
	GDAP1L1	NM_001256739.3		c.199G>T	p.Glu67*	stop_gained	Exon 2 of 5	NP_001243668.1	B7Z1I3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDAP1L1	ENST00000342560.10	TSL:1 MANE Select	c.199G>T	p.Glu67*	stop_gained	Exon 2 of 6	ENSP00000341782.5	Q96MZ0-1
	GDAP1L1	ENST00000537864.5	TSL:2	c.199G>T	p.Glu67*	stop_gained	Exon 2 of 6	ENSP00000440498.2	Q96MZ0-4
	GDAP1L1	ENST00000902255.1		c.199G>T	p.Glu67*	stop_gained	Exon 2 of 6	ENSP00000572314.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1445960 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 718386

African (AFR) AF: 0.00 AC: 0 AN: 33168

American (AMR) AF: 0.00 AC: 0 AN: 43018

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25652

East Asian (EAS) AF: 0.00 AC: 0 AN: 38910

South Asian (SAS) AF: 0.00 AC: 0 AN: 84474

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106074

Other (OTH) AF: 0.00 AC: 0 AN: 59758

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.56	D
BayesDel_noAF	Pathogenic	0.57
CADD	Pathogenic	44
DANN	Uncertain	1.0
Eigen	Pathogenic	1.2
Eigen_PC	Pathogenic	1.1
FATHMM_MKL	Pathogenic	0.99	D
PhyloP100		7.6
Vest4		0.44
ClinPred		1.0	D
GERP RS		5.5
Mutation Taster		=12/188	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1000998948; hg19: chr20-42885811;