Variant 3-183825403-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.145C>T(p.Arg49Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MAP6D1
NM_024871.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.208

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:

Genome browser will be placed here

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=0.120331675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP6D1	NM_024871.4 linkuse as main transcript	c.145C>T	p.Arg49Cys	missense_variant	1/3	ENST00000318631.8	NP_079147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MAP6D1	ENST00000318631.8 linkuse as main transcript	c.145C>T	p.Arg49Cys	missense_variant	1/3	1	NM_024871.4	ENSP00000314560	P1
MAP6D1	ENST00000431348.1 linkuse as main transcript	c.145C>T	p.Arg49Cys	missense_variant	1/3	2		ENSP00000388945
MAP6D1	ENST00000445426.1 linkuse as main transcript	c.121C>T	p.Arg41Cys	missense_variant, NMD_transcript_variant	1/3	4		ENSP00000390816

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1291672

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

636010

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 15, 2021

The c.145C>T (p.R49C) 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 145, causing the arginine (R) at amino acid position 49 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

0.16

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.61

T;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.023

Sift

Benign

0.088

T;T

Sift4G

Benign

0.10

T;T

Polyphen

0.0050

B;.

Vest4

0.20

MutPred

0.22

Gain of loop (P = 0.0435);Gain of loop (P = 0.0435);

MVP

0.26

MPC

0.034

ClinPred

0.66

GERP RS

-2.3

Varity_R

0.11

gMVP

0.25

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