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GeneBe

5-94888886-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_024717.7(MCTP1):c.1926C>T(p.Asp642=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00357 in 1,608,120 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 29 hom., cov: 32)
Exomes 𝑓: 0.0027 ( 60 hom. )

Consequence

MCTP1
NM_024717.7 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0510
Variant links:
Genes affected
MCTP1 (HGNC:26183): (multiple C2 and transmembrane domain containing 1) Enables calcium ion binding activity. Predicted to be involved in several processes, including modulation of chemical synaptic transmission; negative regulation of endocytosis; and negative regulation of response to oxidative stress. Is integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-94888886-G-A is Benign according to our data. Variant chr5-94888886-G-A is described in ClinVar as [Benign]. Clinvar id is 768020.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.051 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0118 (1796/152172) while in subpopulation EAS AF= 0.0446 (231/5174). AF 95% confidence interval is 0.0399. There are 29 homozygotes in gnomad4. There are 883 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 29 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MCTP1NM_024717.7 linkuse as main transcriptc.1926C>T p.Asp642= synonymous_variant 12/23 ENST00000515393.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MCTP1ENST00000515393.6 linkuse as main transcriptc.1926C>T p.Asp642= synonymous_variant 12/231 NM_024717.7 P2Q6DN14-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0118
AC:
1796
AN:
152054
Hom.:
29
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0308
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0168
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0447
Gnomad SAS
AF:
0.00124
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00860
GnomAD3 exomes
AF:
0.00788
AC:
1978
AN:
251052
Hom.:
25
AF XY:
0.00632
AC XY:
857
AN XY:
135672
show subpopulations
Gnomad AFR exome
AF:
0.0318
Gnomad AMR exome
AF:
0.0182
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0399
Gnomad SAS exome
AF:
0.00121
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000705
Gnomad OTH exome
AF:
0.00882
GnomAD4 exome
AF:
0.00271
AC:
3948
AN:
1455948
Hom.:
60
Cov.:
29
AF XY:
0.00240
AC XY:
1736
AN XY:
724818
show subpopulations
Gnomad4 AFR exome
AF:
0.0313
Gnomad4 AMR exome
AF:
0.0211
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0360
Gnomad4 SAS exome
AF:
0.00104
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000325
Gnomad4 OTH exome
AF:
0.00653
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0118
AC:
1796
AN:
152172
Hom.:
29
Cov.:
32
AF XY:
0.0119
AC XY:
883
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.0308
Gnomad4 AMR
AF:
0.0167
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0446
Gnomad4 SAS
AF:
0.00124
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00851
Alfa
AF:
0.00238
Hom.:
8
Bravo
AF:
0.0138
Asia WGS
AF:
0.0260
AC:
89
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMay 09, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
Cadd
Benign
0.24
Dann
Benign
0.32

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: rs17084201; hg19: chr5-94224591; API