X-136225925-C-T

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

4
4
9

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]

Genome browser will be placed here

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
MAP7D3NM_024597.4 linkc.2123G>A p.Arg708Gln missense_variant Exon 13 of 19 ENST00000316077.14 NP_078873.2 Q8IWC1-1
MAP7D3NM_001173516.1 linkc.2069G>A p.Arg690Gln missense_variant Exon 13 of 19 NP_001166987.1 Q8IWC1-4
MAP7D3NM_001173517.2 linkc.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
MAP7D3ENST00000316077.14 linkc.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.:
1
Cov.:
22
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.:
2
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.:
14
Cov.:
25
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.:
1
Cov.:
22
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:
10
ALSPAC
AF:
0.00415
AC:
12
ESP6500AA
AF:
0.000637
AC:
2
ESP6500EA
AF:
0.00625
AC:
40
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
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.073
.;T;.;T
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Pathogenic
0.99
D;D;D;D
M_CAP
Benign
0.038
D
MetaRNN
Benign
0.0085
T;T;T;T
MetaSVM
Benign
-0.84
T
MutationAssessor
Pathogenic
3.7
.;H;.;.
PrimateAI
Benign
0.38
T
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
T
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.

Other links and lift over

dbSNP: rs191075892; hg19: chrX-135308084; COSMIC: COSV60170729; COSMIC: COSV60170729; API