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GeneBe

14-60796349-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_002431.4(MNAT1):c.222C>T(p.Ile74=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000637 in 1,611,472 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00048 ( 2 hom. )

Consequence

MNAT1
NM_002431.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.586
Variant links:
Genes affected
MNAT1 (HGNC:7181): (MNAT1 component of CDK activating kinase) The protein encoded by this gene, along with cyclin H and CDK7, forms the CDK-activating kinase (CAK) enzymatic complex. This complex activates several cyclin-associated kinases and can also associate with TFIIH to activate transcription by RNA polymerase II. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 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=-0.39).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 14-60796349-C-T is Benign according to our data. Variant chr14-60796349-C-T is described in ClinVar as [Benign]. Clinvar id is 790144.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=0.586 with no splicing effect.
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 AC in GnomAd at 328 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MNAT1NM_002431.4 linkuse as main transcriptc.222C>T p.Ile74= synonymous_variant 2/8 ENST00000261245.9
MNAT1NM_001177963.2 linkuse as main transcriptc.222C>T p.Ile74= synonymous_variant 2/7
MNAT1XM_017021332.3 linkuse as main transcriptc.177C>T p.Ile59= synonymous_variant 3/9
MNAT1XM_005267688.4 linkuse as main transcriptc.222C>T p.Ile74= synonymous_variant 2/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MNAT1ENST00000261245.9 linkuse as main transcriptc.222C>T p.Ile74= synonymous_variant 2/81 NM_002431.4 P1P51948-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00216
AC:
328
AN:
152096
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00534
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00393
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000397
Gnomad OTH
AF:
0.00670
GnomAD3 exomes
AF:
0.000852
AC:
212
AN:
248870
Hom.:
2
AF XY:
0.000736
AC XY:
99
AN XY:
134498
show subpopulations
Gnomad AFR exome
AF:
0.00532
Gnomad AMR exome
AF:
0.00147
Gnomad ASJ exome
AF:
0.00200
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000998
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000390
Gnomad OTH exome
AF:
0.00148
GnomAD4 exome
AF:
0.000478
AC:
698
AN:
1459258
Hom.:
2
Cov.:
30
AF XY:
0.000468
AC XY:
340
AN XY:
725876
show subpopulations
Gnomad4 AFR exome
AF:
0.00574
Gnomad4 AMR exome
AF:
0.00163
Gnomad4 ASJ exome
AF:
0.00169
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000265
Gnomad4 OTH exome
AF:
0.00109
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00216
AC:
329
AN:
152214
Hom.:
0
Cov.:
32
AF XY:
0.00198
AC XY:
147
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.00534
Gnomad4 AMR
AF:
0.00393
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000397
Gnomad4 OTH
AF:
0.00664
Alfa
AF:
0.00146
Hom.:
0
Bravo
AF:
0.00267
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.000383
EpiControl
AF:
0.000476

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 testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.39
Cadd
Benign
12
Dann
Benign
0.70
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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: rs113043441; hg19: chr14-61263067; API