rs2020892

Positions:

• chr14-60811966-A-G
• chr14-60811966-A-T

Variant summary

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

The NM_002431.4(MNAT1):​c.421-21A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,542,056 control chromosomes in the GnomAD database, including 81,137 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 0.26 (6591 hom., cov: 32)
  • Exomes 𝑓: 0.32 (74546 hom.)
• Consequence: MNAT1 NM_002431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MNAT1	NM_002431.4	c.421-21A>G		intron_variant		ENST00000261245.9	NP_002422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MNAT1	ENST00000261245.9	c.421-21A>G		intron_variant		1	NM_002431.4	ENSP00000261245	P1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39589 AN: 152018 Hom.: 6591 Cov.: 32

Gnomad AFR AF: 0.0711

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.256

GnomAD3 exomes AF: 0.317 AC: 65854 AN: 207846 Hom.: 12276 AF XY: 0.318 AC XY: 35895 AN XY: 112988

Gnomad AFR exome AF: 0.0643

Gnomad AMR exome AF: 0.545

Gnomad ASJ exome AF: 0.241

Gnomad EAS exome AF: 0.0971

Gnomad SAS exome AF: 0.364

Gnomad FIN exome AF: 0.392

Gnomad NFE exome AF: 0.317

Gnomad OTH exome AF: 0.315

GnomAD4 exome AF: 0.318 AC: 442272 AN: 1389922 Hom.: 74546 Cov.: 29 AF XY: 0.319 AC XY: 219892 AN XY: 688880

Gnomad4 AFR exome AF: 0.0575

Gnomad4 AMR exome AF: 0.522

Gnomad4 ASJ exome AF: 0.245

Gnomad4 EAS exome AF: 0.0942

Gnomad4 SAS exome AF: 0.357

Gnomad4 FIN exome AF: 0.384

Gnomad4 NFE exome AF: 0.325

Gnomad4 OTH exome AF: 0.290

GnomAD4 genome AF: 0.260 AC: 39604 AN: 152134 Hom.: 6591 Cov.: 32 AF XY: 0.267 AC XY: 19829 AN XY: 74362

Gnomad4 AFR AF: 0.0709

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.256

Alfa AF: 0.310 Hom.: 7806

Bravo AF: 0.254

Asia WGS AF: 0.259 AC: 901 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.73
DANN	Benign	0.60
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

Other links and lift over

dbSNP: rs2020892; hg19: chr14-61278684; COSMIC: COSV54194353; COSMIC: COSV54194353;