X-136225967-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_024597.4(MAP7D3):​c.2081A>G​(p.Lys694Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 1,204,925 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 42 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 22)
Exomes 𝑓: 0.00017 ( 0 hom. 41 hem. )

Consequence

MAP7D3
NM_024597.4 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18
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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.10822013).
BS2
High Hemizygotes in GnomAdExome4 at 41 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAP7D3NM_024597.4 linkc.2081A>G p.Lys694Arg missense_variant Exon 13 of 19 ENST00000316077.14 NP_078873.2 Q8IWC1-1
MAP7D3NM_001173516.1 linkc.2027A>G p.Lys676Arg missense_variant Exon 13 of 19 NP_001166987.1 Q8IWC1-4
MAP7D3NM_001173517.2 linkc.1976A>G p.Lys659Arg 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.2081A>G p.Lys694Arg missense_variant Exon 13 of 19 1 NM_024597.4 ENSP00000318086.9 Q8IWC1-1

Frequencies

GnomAD3 genomes
AF:
0.0000179
AC:
2
AN:
111959
Hom.:
0
Cov.:
22
AF XY:
0.0000293
AC XY:
1
AN XY:
34105
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:
0.0000376
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000286
AC:
5
AN:
175014
Hom.:
0
AF XY:
0.0000326
AC XY:
2
AN XY:
61278
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000626
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000166
AC:
181
AN:
1092966
Hom.:
0
Cov.:
27
AF XY:
0.000114
AC XY:
41
AN XY:
358598
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.000212
Gnomad4 OTH exome
AF:
0.0000653
GnomAD4 genome
AF:
0.0000179
AC:
2
AN:
111959
Hom.:
0
Cov.:
22
AF XY:
0.0000293
AC XY:
1
AN XY:
34105
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000376
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000142
Hom.:
1
Bravo
AF:
0.0000189
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000346
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000156
AC:
1
ExAC
AF:
0.0000414
AC:
5

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 29, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2081A>G (p.K694R) alteration is located in exon 13 (coding exon 13) of the MAP7D3 gene. This alteration results from a A to G substitution at nucleotide position 2081, causing the lysine (K) at amino acid position 694 to be replaced by an arginine (R). 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
0.15
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-0.83
CADD
Benign
14
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0013
.;T;.;T
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.69
T;T;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.11
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.71
.;N;.;.
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-0.19
N;N;N;N
REVEL
Benign
0.062
Sift
Benign
0.33
T;T;T;T
Sift4G
Benign
0.94
T;T;T;.
Polyphen
0.99
D;D;.;.
Vest4
0.19
MVP
0.38
MPC
0.37
ClinPred
0.13
T
GERP RS
0.90
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.092
gMVP
0.0096

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs377561911; hg19: chrX-135308126; API