Genetic Variant MAP7D3:p.Arg708Gln (chrX-136225925-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_024597.4(MAP7D3):c.2123G>A(p.Arg708Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00467 in 1,188,264 control chromosomes in the GnomAD database, including 15 homozygotes. There are 1,677 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 1 hom., 103 hem., cov: 22)

Exomes 𝑓: 0.0048 ( 14 hom. 1574 hem. )

Consequence

MAP7D3
NM_024597.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.38

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008494109).

BP6

Variant X-136225925-C-T is Benign according to our data. Variant chrX-136225925-C-T is described in ClinVar as [Benign]. Clinvar id is 719311.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-136225925-C-T is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 103 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP7D3	NM_024597.4 link	c.2123G>A	p.Arg708Gln	missense_variant	Exon 13 of 19	ENST00000316077.14	NP_078873.2	Q8IWC1-1
MAP7D3	NM_001173516.1 link	c.2069G>A	p.Arg690Gln	missense_variant	Exon 13 of 19		NP_001166987.1	Q8IWC1-4
MAP7D3	NM_001173517.2 link	c.2018G>A	p.Arg673Gln	missense_variant	Exon 12 of 18		NP_001166988.1	Q8IWC1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP7D3	ENST00000316077.14 link	c.2123G>A	p.Arg708Gln	missense_variant	Exon 13 of 19	1	NM_024597.4	ENSP00000318086.9		Q8IWC1-1

Frequencies

GnomAD3 genomes

AF:

0.00301

AC:

337

AN:

111815

Hom.:

Cov.:

AF XY:

0.00306

AC XY:

104

AN XY:

34005

show subpopulations

Gnomad AFR

AF:

0.000553

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000475

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0118

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00451

Gnomad OTH

AF:

0.00264

GnomAD3 exomes

AF:

0.00349

AC:

605

AN:

173324

Hom.:

AF XY:

0.00326

AC XY:

195

AN XY:

59836

show subpopulations

Gnomad AFR exome

AF:

0.0000835

Gnomad AMR exome

AF:

0.000118

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000600

Gnomad FIN exome

AF:

0.0125

Gnomad NFE exome

AF:

0.00487

Gnomad OTH exome

AF:

0.00407

GnomAD4 exome

AF:

0.00484

AC:

5208

AN:

1076394

Hom.:

Cov.:

AF XY:

0.00457

AC XY:

1574

AN XY:

344098

show subpopulations

Gnomad4 AFR exome

AF:

0.000347

Gnomad4 AMR exome

AF:

0.000145

Gnomad4 ASJ exome

AF:

0.000104

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000767

Gnomad4 FIN exome

AF:

0.0122

Gnomad4 NFE exome

AF:

0.00548

Gnomad4 OTH exome

AF:

0.00379

GnomAD4 genome

AF:

0.00300

AC:

336

AN:

111870

Hom.:

Cov.:

AF XY:

0.00302

AC XY:

103

AN XY:

34070

show subpopulations

Gnomad4 AFR

AF:

0.000552

Gnomad4 AMR

AF:

0.000475

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0118

Gnomad4 NFE

AF:

0.00450

Gnomad4 OTH

AF:

0.00261

Alfa

AF:

0.00376

Hom.:

155

Bravo

AF:

0.00220

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000637

AC:

ESP6500EA

AF:

0.00625

AC:

ExAC

AF:

0.00337

AC:

407

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

MAP7D3-related disorder

Benign:1

Sep 05, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Pathogenic

0.86

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.073

.;T;.;T

FATHMM_MKL

Uncertain

0.84

LIST_S2

Pathogenic

0.99

D;D;D;D

M_CAP

Benign

0.038

MetaRNN

Benign

0.0085

T;T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Pathogenic

3.7

.;H;.;.

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.6

D;D;D;D

REVEL

Benign

0.17

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Uncertain

0.011

D;D;D;.

Polyphen

1.0

D;D;.;.

Vest4

0.59

MVP

0.37

MPC

0.46

ClinPred

0.47

GERP RS

2.9

Varity_R

0.70

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