rs4151223

Positions:

• chr14-60808948-T-G

Variant summary

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

The NM_002431.4(MNAT1):​c.420+520T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,070 control chromosomes in the GnomAD database, including 4,527 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 0.22 (4527 hom., cov: 32)
  • Exomes 𝑓: 0.33 (0 hom.)
• Consequence: MNAT1 NM_002431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172

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=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MNAT1	NM_002431.4	c.420+520T>G		intron_variant		ENST00000261245.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MNAT1	ENST00000261245.9	c.420+520T>G		intron_variant		1	NM_002431.4	P1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33493 AN: 151946 Hom.: 4525 Cov.: 32

Gnomad AFR AF: 0.0739

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.333 AC: 2 AN: 6 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.220 AC: 33496 AN: 152064 Hom.: 4527 Cov.: 32 AF XY: 0.221 AC XY: 16420 AN XY: 74346

Gnomad4 AFR AF: 0.0738

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.230

Alfa AF: 0.250 Hom.: 667

Bravo AF: 0.209

Asia WGS AF: 0.174 AC: 604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.1
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: rs4151223; hg19: chr14-61275666;