Variant 3-183825262-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024871.4(MAP6D1):c.286C>T(p.Arg96Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000445 in 1,348,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000025 ( 0 hom. )

Consequence

MAP6D1
NM_024871.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.05

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 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=0.14088494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP6D1	NM_024871.4 link	c.286C>T	p.Arg96Cys	missense_variant	1/3	ENST00000318631.8	NP_079147.1	Q9H9H5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP6D1	ENST00000318631.8 link	c.286C>T	p.Arg96Cys	missense_variant	1/3	1	NM_024871.4	ENSP00000314560.4		Q9H9H5
ENSG00000283765	ENST00000639401.1 link	c.1029-7151C>T		intron_variant		5		ENSP00000491227.1		A0A1W2PP11

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000251

AC:

AN:

1196420

Hom.:

Cov.:

AF XY:

0.00000518

AC XY:

AN XY:

579420

show subpopulations

Gnomad4 AFR exome

AF:

0.0000847

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:

0.00

Gnomad4 OTH exome

AF:

0.0000205

GnomAD4 genome

AF:

0.0000197

AC:

AN:

151968

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.0000724

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

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

Dec 03, 2024

The c.286C>T (p.R96C) alteration is located in exon 1 (coding exon 1) of the MAP6D1 gene. This alteration results from a C to T substitution at nucleotide position 286, causing the arginine (R) at amino acid position 96 to be replaced by a cysteine (C). 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

0.24

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.032

T;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.72

T;T

M_CAP

Pathogenic

0.34

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

M;.

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.025

Sift

Uncertain

0.012

D;D

Sift4G

Uncertain

0.025

D;D

Polyphen

0.0080

B;.

Vest4

0.12

MutPred

0.34

Loss of MoRF binding (P = 0.0016);Loss of MoRF binding (P = 0.0016);

MVP

0.29

MPC

0.0086

ClinPred

0.20

GERP RS

0.63

Varity_R

0.13

gMVP

0.26

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