rs2882684

chr14-60949744-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002431.4(MNAT1):c.810-18485A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 152,010 control chromosomes in the GnomAD database, including 29,263 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 0.60 (29263 hom., cov: 33)
• Consequence: MNAT1 NM_002431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920

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

Verdict is Benign. Variant got -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 = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MNAT1	NM_002431.4	c.810-18485A>G		intron_variant		ENST00000261245.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MNAT1	ENST00000261245.9	c.810-18485A>G		intron_variant		1	NM_002431.4	P1
MNAT1	ENST00000539616.6	c.684-18485A>G		intron_variant		1
MNAT1	ENST00000554002.5	c.495-18815A>G		intron_variant		3
MNAT1	ENST00000557134.1	c.390-18485A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91677 AN: 151892 Hom.: 29277 Cov.: 33

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.710

Gnomad OTH AF: 0.630

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

GnomAD4 genome AF: 0.603 AC: 91683 AN: 152010 Hom.: 29263 Cov.: 33 AF XY: 0.603 AC XY: 44812 AN XY: 74294

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.647

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.721

Gnomad4 NFE AF: 0.709

Gnomad4 OTH AF: 0.626

Alfa AF: 0.662 Hom.: 11031

Bravo AF: 0.591

Asia WGS AF: 0.580 AC: 2005 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.6
Dann	Benign	0.42

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

Other links and lift over

dbSNP: rs2882684; hg19: chr14-61416462;