Genetic Variant MAP7D3:p.Arg623Gln (chrX-136228641-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_024597.4(MAP7D3):c.1868G>A(p.Arg623Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000813 in 1,205,706 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 39 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R623W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000071 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.000082 ( 0 hom. 37 hem. )

Consequence

MAP7D3
NM_024597.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.170

Publications

1 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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026488692).

BP6

Variant X-136228641-C-T is Benign according to our data. Variant chrX-136228641-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3870401.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

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.1868G>A	p.Arg623Gln	missense	Exon 11 of 19	NP_078873.2
MAP7D3	NM_001173516.1		c.1814G>A	p.Arg605Gln	missense	Exon 11 of 19	NP_001166987.1	Q8IWC1-4
MAP7D3	NM_001173517.2		c.1763G>A	p.Arg588Gln	missense	Exon 10 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.1868G>A	p.Arg623Gln	missense	Exon 11 of 19	ENSP00000318086.9	Q8IWC1-1
MAP7D3	ENST00000370661.5	TSL:1	c.1763G>A	p.Arg588Gln	missense	Exon 10 of 18	ENSP00000359695.1	Q8IWC1-3
MAP7D3	ENST00000370660.3	TSL:1	c.1745G>A	p.Arg582Gln	missense	Exon 11 of 17	ENSP00000359694.3	A0A0A0MRP0

Frequencies

GnomAD3 genomes

AF:

0.0000714

AC:

AN:

112092

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:

0.000150

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000579

AC:

AN:

172842

AF XY:

0.0000841

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:

0.000127

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000823

AC:

AN:

1093614

Hom.:

Cov.:

AF XY:

0.000103

AC XY:

AN XY:

359534

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26218

American (AMR)

AF:

0.00

AC:

AN:

34413

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19293

East Asian (EAS)

AF:

0.00

AC:

AN:

29784

South Asian (SAS)

AF:

0.00

AC:

AN:

53106

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40461

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4113

European-Non Finnish (NFE)

AF:

0.000100

AC:

AN:

840274

Other (OTH)

AF:

0.000131

AC:

AN:

45952

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000714

AC:

AN:

112092

Hom.:

Cov.:

AF XY:

0.0000584

AC XY:

AN XY:

34248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30814

American (AMR)

AF:

0.00

AC:

AN:

10551

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2648

East Asian (EAS)

AF:

0.00

AC:

AN:

3596

South Asian (SAS)

AF:

0.00

AC:

AN:

2715

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6077

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.000150

AC:

AN:

53266

Other (OTH)

AF:

0.00

AC:

AN:

1503

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Hom

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:

0.000217

Hom.:

Bravo

AF:

0.0000642

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000346

AC:

ExAC

AF:

0.0000579

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.10

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.062

(source)

DANN

Benign

0.54

DEOGEN2

Benign

0.0018

FATHMM_MKL

Benign

0.00063

LIST_S2

Benign

0.57

M_CAP

Benign

0.0055

MetaRNN

Benign

0.026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

PhyloP100

0.17

PrimateAI

Benign

0.20

PROVEAN

Benign

1.3

REVEL

Benign

0.015

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.11

Vest4

0.16

MVP

0.28

MPC

0.089

ClinPred

0.022

GERP RS

-2.3

Varity_R

0.027

gMVP

0.0077

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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