Genetic Variant MAP7D3:p.Arg799Cys (chrX-136220856-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_024597.4(MAP7D3):c.2395C>T(p.Arg799Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,202,188 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.0000083 ( 0 hom. 2 hem. )

Consequence

MAP7D3
NM_024597.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.52

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.037302613).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP7D3	NM_024597.4 link	c.2395C>T	p.Arg799Cys	missense_variant	Exon 16 of 19	ENST00000316077.14	NP_078873.2	Q8IWC1-1
MAP7D3	NM_001173516.1 link	c.2341C>T	p.Arg781Cys	missense_variant	Exon 16 of 19		NP_001166987.1	Q8IWC1-4
MAP7D3	NM_001173517.2 link	c.2290C>T	p.Arg764Cys	missense_variant	Exon 15 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.2395C>T	p.Arg799Cys	missense_variant	Exon 16 of 19	1	NM_024597.4	ENSP00000318086.9		Q8IWC1-1

Frequencies

GnomAD3 genomes

AF:

0.0000537

AC:

AN:

111724

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33936

show subpopulations

Gnomad AFR

AF:

0.000195

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000165

AC:

AN:

181706

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67558

show subpopulations

Gnomad AFR exome

AF:

0.000242

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000825

AC:

AN:

1090464

Hom.:

Cov.:

AF XY:

0.00000562

AC XY:

AN XY:

355954

show subpopulations

Gnomad4 AFR exome

AF:

0.0000761

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000838

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000537

AC:

AN:

111724

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33936

show subpopulations

Gnomad4 AFR

AF:

0.000195

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2395C>T (p.R799C) alteration is located in exon 16 (coding exon 16) of the MAP7D3 gene. This alteration results from a C to T substitution at nucleotide position 2395, causing the arginine (R) at amino acid position 799 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.60

DANN

Benign

0.70

DEOGEN2

Benign

0.014

.;T;.;T

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.54

T;T;T;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.037

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.55

.;N;.;.

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Benign

0.18

Sift

Benign

0.10

T;T;T;T

Sift4G

Benign

0.19

T;T;T;.

Polyphen

0.0010

B;B;.;.

Vest4

0.060

MVP

0.23

MPC

0.10

ClinPred

0.019

GERP RS

-5.4

Varity_R

0.052

gMVP

0.036

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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