Variant 14-60811997-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002431.4(MNAT1):c.431A>G(p.Gln144Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000303 in 1,585,318 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

MNAT1
NM_002431.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.66

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]

MNAT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MNAT1	NM_002431.4 linkuse as main transcript	c.431A>G	p.Gln144Arg	missense_variant	5/8	ENST00000261245.9	NP_002422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MNAT1	ENST00000261245.9 linkuse as main transcript	c.431A>G	p.Gln144Arg	missense_variant	5/8	1	NM_002431.4	ENSP00000261245	P1	P51948-1

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000265

AC:

AN:

226776

Hom.:

AF XY:

0.0000244

AC XY:

AN XY:

122862

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:

0.0000559

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000300

AC:

AN:

1433082

Hom.:

Cov.:

AF XY:

0.0000267

AC XY:

AN XY:

712050

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:

0.0000371

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000676

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2022

The c.431A>G (p.Q144R) alteration is located in exon 5 (coding exon 5) of the MNAT1 gene. This alteration results from a A to G substitution at nucleotide position 431, causing the glutamine (Q) at amino acid position 144 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

Uncertain

0.47

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;.;T;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D;D;T

M_CAP

Benign

0.016

MetaRNN

Uncertain

0.50

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.9

L;L;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-2.4

N;N;D;N

REVEL

Benign

0.15

Sift

Benign

0.11

T;T;D;D

Sift4G

Benign

0.26

T;T;D;D

Polyphen

0.92

P;.;.;.

Vest4

0.75

MutPred

0.47

Gain of MoRF binding (P = 0.0604);Gain of MoRF binding (P = 0.0604);.;.;

MVP

0.78

MPC

0.89

ClinPred

0.40

GERP RS

5.6

Varity_R

0.48

gMVP

0.66

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over