rs973063

chr14-60818634-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.562-88A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 1,180,028 control chromosomes in the GnomAD database, including 210,641 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 0.48 (21155 hom., cov: 32)
  • Exomes 𝑓: 0.60 (189486 hom.)
• Consequence: MNAT1 NM_002431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MNAT1	NM_002431.4	c.562-88A>G		intron_variant		ENST00000261245.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MNAT1	ENST00000261245.9	c.562-88A>G		intron_variant		1	NM_002431.4	P1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72617 AN: 151840 Hom.: 21150 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.474

GnomAD4 exome AF: 0.596 AC: 613112 AN: 1028070 Hom.: 189486 AF XY: 0.596 AC XY: 301427 AN XY: 506004

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.691

Gnomad4 ASJ exome AF: 0.583

Gnomad4 EAS exome AF: 0.248

Gnomad4 SAS exome AF: 0.531

Gnomad4 FIN exome AF: 0.688

Gnomad4 NFE exome AF: 0.626

Gnomad4 OTH exome AF: 0.553

GnomAD4 genome AF: 0.478 AC: 72641 AN: 151958 Hom.: 21155 Cov.: 32 AF XY: 0.484 AC XY: 35962 AN XY: 74272

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.625

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.524

Gnomad4 FIN AF: 0.696

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.472

Alfa AF: 0.528 Hom.: 4476

Bravo AF: 0.460

Asia WGS AF: 0.393 AC: 1366 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	13
Dann	Benign	0.78

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: rs973063; hg19: chr14-61285352;