rs370507208

Variant names:

• chr20-44264556-G-C
• rs370507208
• NM_024034.6:c.757G>C

Your query was ambiguous. Multiple possible variants found:

• chr20-44264556-G-C
• chr20-44264556-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024034.6(GDAP1L1):​c.757G>C​(p.Glu253Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000165 in 1,458,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: GDAP1L1 NM_024034.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.22
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16327292).

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.757G>C	p.Glu253Gln	missense	Exon 5 of 6	NP_076939.3
	GDAP1L1	NM_001256737.2		c.814G>C	p.Glu272Gln	missense	Exon 5 of 6	NP_001243666.1	Q96MZ0-4
	GDAP1L1	NM_001256739.3		c.583G>C	p.Glu195Gln	missense	Exon 4 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.757G>C	p.Glu253Gln	missense	Exon 5 of 6	ENSP00000341782.5	Q96MZ0-1
	GDAP1L1	ENST00000537864.5	TSL:2	c.814G>C	p.Glu272Gln	missense	Exon 5 of 6	ENSP00000440498.2	Q96MZ0-4
	GDAP1L1	ENST00000902255.1		c.748G>C	p.Glu250Gln	missense	Exon 5 of 6	ENSP00000572314.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 248408 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000891

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000165 AC: 24 AN: 1458236 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 725288

African (AFR) AF: 0.00 AC: 0 AN: 33400

American (AMR) AF: 0.00 AC: 0 AN: 44424

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25960

East Asian (EAS) AF: 0.00 AC: 0 AN: 39582

South Asian (SAS) AF: 0.00 AC: 0 AN: 85804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1109910

Other (OTH) AF: 0.00 AC: 0 AN: 60218

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.0047
Eigen_PC	Benign	0.037
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.14	N
PhyloP100		2.2
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.030	N
REVEL	Uncertain	0.29
Sift	Benign	0.27	T
Sift4G	Benign	0.81	T
Polyphen		0.0010	B
Vest4		0.18
MutPred		0.36		Loss of helix (P = 0.0093)
MVP		0.94
MPC		0.47
ClinPred		0.12	T
GERP RS		2.0
PromoterAI		-0.019	Neutral
Varity_R		0.043
gMVP		0.13
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs370507208; hg19: chr20-42893196;