rs3783819

Variant names:

• chr14-60849546-A-G
• rs3783819
• NM_002431.4:c.688-30168A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002431.4(MNAT1):​c.688-30168A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 152,050 control chromosomes in the GnomAD database, including 20,218 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (20218 hom., cov: 32)
• Consequence: MNAT1 NM_002431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 12 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MNAT1	NM_002431.4	c.688-30168A>G		intron_variant	Intron 6 of 7	ENST00000261245.9	NP_002422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MNAT1	ENST00000261245.9	c.688-30168A>G		intron_variant	Intron 6 of 7	1	NM_002431.4	ENSP00000261245.4

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70605 AN: 151932 Hom.: 20214 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.458

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.464 AC: 70625 AN: 152050 Hom.: 20218 Cov.: 32 AF XY: 0.471 AC XY: 34973 AN XY: 74328

African (AFR) AF: 0.122 AC: 5070 AN: 41522

American (AMR) AF: 0.611 AC: 9321 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2039 AN: 3468

East Asian (EAS) AF: 0.266 AC: 1374 AN: 5170

South Asian (SAS) AF: 0.530 AC: 2551 AN: 4814

European-Finnish (FIN) AF: 0.674 AC: 7113 AN: 10552

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.611 AC: 41516 AN: 67946

Other (OTH) AF: 0.457 AC: 965 AN: 2112

Alfa AF: 0.554 Hom.: 66868

Bravo AF: 0.447

Asia WGS AF: 0.398 AC: 1384 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.52
PhyloP100		0.036
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3783819; hg19: chr14-61316264;