X-136219623-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_024597.4(MAP7D3):​c.2535G>A​(p.Ala845Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 1,206,522 control chromosomes in the GnomAD database, including 1 homozygotes. There are 66 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., 5 hem., cov: 23)
Exomes 𝑓: 0.00017 ( 1 hom. 61 hem. )

Consequence

MAP7D3
NM_024597.4 synonymous

Scores

2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.29
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 -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant X-136219623-C-T is Benign according to our data. Variant chrX-136219623-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3045196.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-1.29 with no splicing effect.
BS2
High Hemizygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAP7D3NM_024597.4 linkc.2535G>A p.Ala845Ala synonymous_variant Exon 17 of 19 ENST00000316077.14 NP_078873.2 Q8IWC1-1
MAP7D3NM_001173516.1 linkc.2481G>A p.Ala827Ala synonymous_variant Exon 17 of 19 NP_001166987.1 Q8IWC1-4
MAP7D3NM_001173517.2 linkc.2430G>A p.Ala810Ala synonymous_variant Exon 16 of 18 NP_001166988.1 Q8IWC1-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAP7D3ENST00000316077.14 linkc.2535G>A p.Ala845Ala synonymous_variant Exon 17 of 19 1 NM_024597.4 ENSP00000318086.9 Q8IWC1-1

Frequencies

GnomAD3 genomes
AF:
0.000161
AC:
18
AN:
111991
Hom.:
0
Cov.:
23
AF XY:
0.000146
AC XY:
5
AN XY:
34185
show subpopulations
Gnomad AFR
AF:
0.0000650
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000368
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000282
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000716
AC:
13
AN:
181464
Hom.:
0
AF XY:
0.0000297
AC XY:
2
AN XY:
67334
show subpopulations
Gnomad AFR exome
AF:
0.000161
Gnomad AMR exome
AF:
0.0000365
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000738
Gnomad SAS exome
AF:
0.0000525
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000984
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000173
AC:
189
AN:
1094479
Hom.:
1
Cov.:
29
AF XY:
0.000169
AC XY:
61
AN XY:
360075
show subpopulations
Gnomad4 AFR exome
AF:
0.0000758
Gnomad4 AMR exome
AF:
0.0000284
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000331
Gnomad4 SAS exome
AF:
0.0000185
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000203
Gnomad4 OTH exome
AF:
0.000304
GnomAD4 genome
AF:
0.000161
AC:
18
AN:
112043
Hom.:
0
Cov.:
23
AF XY:
0.000146
AC XY:
5
AN XY:
34247
show subpopulations
Gnomad4 AFR
AF:
0.0000648
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000370
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000282
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000142
Hom.:
1
Bravo
AF:
0.000140
EpiCase
AF:
0.000109
EpiControl
AF:
0.000358

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

MAP7D3-related disorder Benign:1
Nov 07, 2019
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as likely 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
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.17
DANN
Benign
0.38
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
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: rs370445924; hg19: chrX-135301782; COSMIC: COSV60171063; COSMIC: COSV60171063; API