Variant 3-183825397-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024871.4(MAP6D1):c.151G>C(p.Gly51Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000691 in 1,447,172 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: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000076 ( 0 hom. )

Consequence

MAP6D1
NM_024871.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.91

Variant links:

Genes affected

MAP6D1 (HGNC:25753): (MAP6 domain containing 1) This gene encodes a protein highly similar to the mouse MAP6 domain containing 1 protein, which is related to the STOP proteins. Based on the study of the mouse protein, the encoded protein may function as a calmodulin-regulated neuronal protein that binds and stabilizes microtubules but also associates with the Golgi membranes through N-terminal palmitoylation. [provided by RefSeq, Oct 2008]

MAP6D1 links:

ENSG00000283765 (HGNC:):

ENSG00000283765 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052046537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP6D1	NM_024871.4 linkuse as main transcript	c.151G>C	p.Gly51Arg	missense_variant	1/3	ENST00000318631.8	NP_079147.1	Q9H9H5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MAP6D1	ENST00000318631.8 linkuse as main transcript	c.151G>C	p.Gly51Arg	missense_variant	1/3	1	NM_024871.4	ENSP00000314560.4	Q9H9H5
ENSG00000283765	ENST00000639401.1 linkuse as main transcript	c.1029-7286G>C		intron_variant		5		ENSP00000491227.1	A0A1W2PP11
MAP6D1	ENST00000431348.1 linkuse as main transcript	c.151G>C	p.Gly51Arg	missense_variant	1/3	2		ENSP00000388945.1	C9JPF8
MAP6D1	ENST00000445426.1 linkuse as main transcript	n.124G>C		non_coding_transcript_exon_variant	1/3	4		ENSP00000390816.1	H7BZQ6

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151542

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

62590

Hom.:

AF XY:

0.0000275

AC XY:

AN XY:

36400

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000452

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000756

AC:

AN:

1295630

Hom.:

Cov.:

AF XY:

0.0000595

AC XY:

AN XY:

638124

show subpopulations

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:

0.0000927

Gnomad4 OTH exome

AF:

0.0000376

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151542

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74018

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 26, 2024

The c.151G>C (p.G51R) alteration is located in exon 1 (coding exon 1) of the MAP6D1 gene. This alteration results from a G to C substitution at nucleotide position 151, causing the glycine (G) at amino acid position 51 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.65

CADD

Benign

9.8

DANN

Benign

0.64

DEOGEN2

Benign

0.0092

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.49

T;T

M_CAP

Benign

0.069

MetaRNN

Benign

0.052

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.46

N;.

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.19

N;N

REVEL

Benign

0.011

Sift

Benign

0.17

T;T

Sift4G

Benign

0.78

T;T

Polyphen

0.0030

B;.

Vest4

0.080

MutPred

0.18

Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);

MVP

0.13

MPC

0.020

ClinPred

0.047

GERP RS

0.47

Varity_R

0.040

gMVP

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over