14-60811966-A-G

Variant names:

• chr14-60811966-A-G
• rs2020892
• NM_002431.4:c.421-21A>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.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
• Publications: 15 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002431.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MNAT1	NM_002431.4	MANE Select	c.421-21A>G		intron	N/A	NP_002422.1
	MNAT1	NM_001177963.2		c.421-21A>G		intron	N/A	NP_001171434.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MNAT1	ENST00000261245.9	TSL:1 MANE Select	c.421-21A>G		intron	N/A	ENSP00000261245.4
	MNAT1	ENST00000539616.6	TSL:1	c.421-21A>G		intron	N/A	ENSP00000446437.2
	MNAT1	ENST00000931367.1		c.421-21A>G		intron	N/A	ENSP00000601426.1

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

GnomAD2 exomes AF: 0.317 AC: 65854 AN: 207846 AF XY: 0.318

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 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

African (AFR) AF: 0.0575 AC: 1759 AN: 30566

American (AMR) AF: 0.522 AC: 16877 AN: 32306

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 5695 AN: 23288

East Asian (EAS) AF: 0.0942 AC: 3650 AN: 38728

South Asian (SAS) AF: 0.357 AC: 25087 AN: 70338

European-Finnish (FIN) AF: 0.384 AC: 19535 AN: 50884

Middle Eastern (MID) AF: 0.211 AC: 1148 AN: 5452

European-Non Finnish (NFE) AF: 0.325 AC: 351888 AN: 1081100

Other (OTH) AF: 0.290 AC: 16633 AN: 57260

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

African (AFR) AF: 0.0709 AC: 2945 AN: 41548

American (AMR) AF: 0.409 AC: 6252 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 871 AN: 3472

East Asian (EAS) AF: 0.103 AC: 535 AN: 5188

South Asian (SAS) AF: 0.357 AC: 1721 AN: 4814

European-Finnish (FIN) AF: 0.393 AC: 4155 AN: 10560

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22187 AN: 67954

Other (OTH) AF: 0.256 AC: 541 AN: 2112

Alfa AF: 0.307 Hom.: 12564

Bravo AF: 0.254

Asia WGS AF: 0.259 AC: 901 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.73
DANN	Benign	0.60
PhyloP100		-1.1
PromoterAI		-0.0082	Neutral
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: rs2020892; hg19: chr14-61278684; COSMIC: COSV54194353; COSMIC: COSV54194353;