3-183825244-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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

Publications

3 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 31 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024871.4. 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
	MAP6D1	NM_024871.4	MANE Select	c.304G>A	p.Ala102Thr	missense	Exon 1 of 3	NP_079147.1	Q9H9H5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAP6D1	ENST00000318631.8	TSL:1 MANE Select	c.304G>A	p.Ala102Thr	missense	Exon 1 of 3	ENSP00000314560.4	Q9H9H5
ENSG00000283765	ENST00000639401.1	TSL:5	c.1029-7133G>A		intron	N/A	ENSP00000491227.1	A0A1W2PP11
MAP6D1	ENST00000933005.1		c.304G>A	p.Ala102Thr	missense	Exon 1 of 4	ENSP00000603064.1

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

GnomAD2 exomes

AF:

0.00195

AC:

AN:

22518

AF XY:

0.00149

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 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

African (AFR)

AF:

0.0454

AC:

1112

AN:

24482

American (AMR)

AF:

0.00290

AC:

AN:

12078

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17904

East Asian (EAS)

AF:

0.00

AC:

AN:

27424

South Asian (SAS)

AF:

0.0000976

AC:

AN:

51252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41416

Middle Eastern (MID)

AF:

0.00165

AC:

AN:

4838

European-Non Finnish (NFE)

AF:

0.0000580

AC:

AN:

1000840

Other (OTH)

AF:

0.00315

AC:

158

AN:

50190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

159

239

318

398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0114

AC:

1730

AN:

152136

Hom.:

Cov.:

AF XY:

0.0111

AC XY:

823

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0396

AC:

1647

AN:

41556

American (AMR)

AF:

0.00432

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000195

AC:

AN:

5132

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67958

Other (OTH)

AF:

0.00473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

166

248

331

414

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00853

Hom.:

Bravo

AF:

0.0131

ExAC

AF:

0.00160

AC:

Asia WGS

AF:

0.00405

AC:

AN:

3468

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

MAP6D1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.0088

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

PhyloP100

0.21

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.1

REVEL

Benign

0.060

Sift

Uncertain

0.018

Sift4G

Benign

0.10

Polyphen

0.99

Vest4

0.067

MVP

0.19

MPC

0.035

ClinPred

0.025

GERP RS

0.15

PromoterAI

-0.041

Neutral

(source)

Varity_R

0.16

gMVP

0.13

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over