Genetic Variant MAP7D3:p.Asp672Glu (chrX-136227302-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024597.4(MAP7D3):c.2016C>G(p.Asp672Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000581 in 1,205,649 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 21)

Exomes 𝑓: 0.0000046 ( 0 hom. 0 hem. )

Consequence

MAP7D3
NM_024597.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.429

Publications

0 publications found

Variant links:

Genes affected

MAP7D3 (HGNC:25742): (MAP7 domain containing 3) The protein encoded by this gene belongs to the MAP7 (microtubule-associated protein 7) family. Alternatively spliced transcript variants encoding different isoforms have been found. [provided by RefSeq, Mar 2010]

MAP7D3 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

MAP7D3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07472107).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024597.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAP7D3	NM_024597.4	MANE Select	c.2016C>G	p.Asp672Glu	missense	Exon 12 of 19	NP_078873.2
MAP7D3	NM_001173516.1		c.1962C>G	p.Asp654Glu	missense	Exon 12 of 19	NP_001166987.1	Q8IWC1-4
MAP7D3	NM_001173517.2		c.1911C>G	p.Asp637Glu	missense	Exon 11 of 18	NP_001166988.1	Q8IWC1-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAP7D3	ENST00000316077.14	TSL:1 MANE Select	c.2016C>G	p.Asp672Glu	missense	Exon 12 of 19	ENSP00000318086.9	Q8IWC1-1
MAP7D3	ENST00000370661.5	TSL:1	c.1911C>G	p.Asp637Glu	missense	Exon 11 of 18	ENSP00000359695.1	Q8IWC1-3
MAP7D3	ENST00000370660.3	TSL:1	c.1893C>G	p.Asp631Glu	missense	Exon 12 of 17	ENSP00000359694.3	A0A0A0MRP0

Frequencies

GnomAD3 genomes

AF:

0.0000185

AC:

AN:

108164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000382

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000552

AC:

AN:

181314

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000456

AC:

AN:

1097485

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362859

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26383

American (AMR)

AF:

0.00

AC:

AN:

35181

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19369

East Asian (EAS)

AF:

0.00

AC:

AN:

30181

South Asian (SAS)

AF:

0.00

AC:

AN:

54097

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40506

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4135

European-Non Finnish (NFE)

AF:

0.00000594

AC:

AN:

841564

Other (OTH)

AF:

0.00

AC:

AN:

46069

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000185

AC:

AN:

108164

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

30500

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29707

American (AMR)

AF:

0.00

AC:

AN:

9940

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2612

East Asian (EAS)

AF:

0.00

AC:

AN:

3405

South Asian (SAS)

AF:

0.00

AC:

AN:

2414

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5312

Middle Eastern (MID)

AF:

0.00

AC:

AN:

230

European-Non Finnish (NFE)

AF:

0.0000382

AC:

AN:

52407

Other (OTH)

AF:

0.00

AC:

AN:

1457

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.96

CADD

Benign

6.8

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0013

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.39

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.075

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.51

PhyloP100

-0.43

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.93

REVEL

Benign

0.074

Sift

Benign

0.21

Sift4G

Benign

1.0

Polyphen

0.95

Vest4

0.11

MutPred

0.26

Gain of MoRF binding (P = 0.227)

MVP

0.38

MPC

0.29

ClinPred

0.24

GERP RS

-7.5

Varity_R

0.14

gMVP

0.0059

Mutation Taster

=99/1

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