rs141872493

Variant names:

• chr20-44258511-G-A
• rs141872493
• NM_024034.6:c.451G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-44258511-G-A
• chr20-44258511-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024034.6(GDAP1L1):​c.451G>A​(p.Ala151Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000252 in 1,568,454 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.000098 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00027 (1 hom.)
• Consequence: GDAP1L1 NM_024034.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.02
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07793707).

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.451G>A	p.Ala151Thr	missense	Exon 3 of 6	NP_076939.3
	GDAP1L1	NM_001256737.2		c.508G>A	p.Ala170Thr	missense	Exon 3 of 6	NP_001243666.1	Q96MZ0-4
	GDAP1L1	NM_001256740.2		c.451G>A	p.Ala151Thr	missense	Exon 3 of 4	NP_001243669.1	A0A087WWT8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDAP1L1	ENST00000342560.10	TSL:1 MANE Select	c.451G>A	p.Ala151Thr	missense	Exon 3 of 6	ENSP00000341782.5	Q96MZ0-1
	GDAP1L1	ENST00000537864.5	TSL:2	c.508G>A	p.Ala170Thr	missense	Exon 3 of 6	ENSP00000440498.2	Q96MZ0-4
	GDAP1L1	ENST00000902255.1		c.451G>A	p.Ala151Thr	missense	Exon 3 of 6	ENSP00000572314.1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000291 AC: 52 AN: 178698 AF XY: 0.000407

Gnomad AFR exome AF: 0.000194

Gnomad AMR exome AF: 0.0000725

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000754

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000163

Gnomad OTH exome AF: 0.000419

GnomAD4 exome AF: 0.000268 AC: 380 AN: 1416164 Hom.: 1 Cov.: 32 AF XY: 0.000291 AC XY: 204 AN XY: 700364

African (AFR) AF: 0.000311 AC: 10 AN: 32178

American (AMR) AF: 0.0000779 AC: 3 AN: 38534

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25290

East Asian (EAS) AF: 0.00 AC: 0 AN: 36838

South Asian (SAS) AF: 0.00113 AC: 91 AN: 80352

European-Finnish (FIN) AF: 0.0000609 AC: 3 AN: 49268

Middle Eastern (MID) AF: 0.00157 AC: 9 AN: 5722

European-Non Finnish (NFE) AF: 0.000235 AC: 256 AN: 1089318

Other (OTH) AF: 0.000136 AC: 8 AN: 58664

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152290 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74456

African (AFR) AF: 0.0000481 AC: 2 AN: 41556

American (AMR) AF: 0.0000653 AC: 1 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68012

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000199 Hom.: 0

Bravo AF: 0.0000982

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000150 AC: 18

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	0.070
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0096	T
Eigen	Benign	-0.049
Eigen_PC	Benign	-0.011
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.0
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.57	N
REVEL	Uncertain	0.30
Sift	Benign	0.12	T
Sift4G	Benign	0.078	T
Polyphen		0.043	B
Vest4		0.18
MVP		0.94
MPC		0.47
ClinPred		0.017	T
GERP RS		2.0
Varity_R		0.057
gMVP		0.22
Mutation Taster		=97/3	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: rs141872493; hg19: chr20-42887151;