rs973063

Variant names:

• chr14-60818634-A-G
• rs973063
• NM_002431.4:c.562-88A>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.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
• Publications: 14 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=-0.78).
• 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 rank	MANE	Protein	UniProt
MNAT1	NM_002431.4	c.562-88A>G		intron_variant	Intron 5 of 7	ENST00000261245.9	NP_002422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MNAT1	ENST00000261245.9	c.562-88A>G		intron_variant	Intron 5 of 7	1	NM_002431.4	ENSP00000261245.4

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

African (AFR) AF: 0.116 AC: 2778 AN: 23988

American (AMR) AF: 0.691 AC: 15239 AN: 22060

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 9794 AN: 16794

East Asian (EAS) AF: 0.248 AC: 8805 AN: 35448

South Asian (SAS) AF: 0.531 AC: 20613 AN: 38800

European-Finnish (FIN) AF: 0.688 AC: 25777 AN: 37462

Middle Eastern (MID) AF: 0.459 AC: 2030 AN: 4420

European-Non Finnish (NFE) AF: 0.626 AC: 504209 AN: 805944

Other (OTH) AF: 0.553 AC: 23867 AN: 43154

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

African (AFR) AF: 0.139 AC: 5783 AN: 41530

American (AMR) AF: 0.625 AC: 9527 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2064 AN: 3468

East Asian (EAS) AF: 0.265 AC: 1373 AN: 5176

South Asian (SAS) AF: 0.524 AC: 2531 AN: 4826

European-Finnish (FIN) AF: 0.696 AC: 7357 AN: 10574

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42326 AN: 67824

Other (OTH) AF: 0.472 AC: 994 AN: 2106

Alfa AF: 0.518 Hom.: 8198

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
PhyloP100		1.3
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: rs973063; hg19: chr14-61285352; COSMIC: COSV107201098;