Variant 3-183825244-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_024871.4(MAP6D1):c.304G>A(p.Ala102Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 1,382,560 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A102V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.011 ( 31 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 34 hom. )

Consequence

MAP6D1
NM_024871.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.210

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002127707).

BP6

Variant 3-183825244-C-T is Benign according to our data. Variant chr3-183825244-C-T is described in ClinVar as [Benign]. Clinvar id is 3353006.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1730/152136) while in subpopulation AFR AF= 0.0396 (1647/41556). AF 95% confidence interval is 0.038. There are 31 homozygotes in gnomad4. There are 823 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP6D1	NM_024871.4 linkuse as main transcript	c.304G>A	p.Ala102Thr	missense_variant	1/3	ENST00000318631.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MAP6D1	ENST00000318631.8 linkuse as main transcript	c.304G>A	p.Ala102Thr	missense_variant	1/3	1	NM_024871.4	P1
MAP6D1	ENST00000431348.1 linkuse as main transcript	c.304G>A	p.Ala102Thr	missense_variant	1/3	2
MAP6D1	ENST00000445426.1 linkuse as main transcript	c.280G>A	p.Ala94Thr	missense_variant, NMD_transcript_variant	1/3	4
MAP6D1	ENST00000463801.1 linkuse as main transcript			upstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0113

AC:

1718

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0395

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00195

AC:

AN:

22518

Hom.:

AF XY:

0.00149

AC XY:

AN XY:

12730

show subpopulations

Gnomad AFR exome

AF:

0.0789

Gnomad AMR exome

AF:

0.00399

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000346

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00437

GnomAD4 exome

AF:

0.00112

AC:

1376

AN:

1230424

Hom.:

Cov.:

AF XY:

0.000922

AC XY:

553

AN XY:

599708

show subpopulations

Gnomad4 AFR exome

AF:

0.0454

Gnomad4 AMR exome

AF:

0.00290

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000976

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000580

Gnomad4 OTH exome

AF:

0.00315

GnomAD4 genome

AF:

0.0114

AC:

1730

AN:

152136

Hom.:

Cov.:

AF XY:

0.0111

AC XY:

823

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0396

Gnomad4 AMR

AF:

0.00432

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000736

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00853

Hom.:

Bravo

AF:

0.0131

ExAC

AF:

0.00160

AC:

Asia WGS

AF:

0.00405

AC:

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MAP6D1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 10, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.0088

T;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.46

T;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.060

Sift

Uncertain

0.018

D;D

Sift4G

Benign

0.10

T;T

Polyphen

0.99

D;.

Vest4

0.067

MVP

0.19

MPC

0.035

ClinPred

0.025

GERP RS

0.15

Varity_R

0.16

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