14-60904827-A-G

Position:

• chr14-60904827-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.809+24992A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 151,876 control chromosomes in the GnomAD database, including 6,231 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 0.27 (6231 hom., cov: 31)
• Consequence: MNAT1 NM_002431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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 (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MNAT1	NM_002431.4	c.809+24992A>G		intron_variant		ENST00000261245.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MNAT1	ENST00000261245.9	c.809+24992A>G		intron_variant		1	NM_002431.4	P1
MNAT1	ENST00000539616.6	c.683+24992A>G		intron_variant		1
MNAT1	ENST00000554002.5	c.494+24992A>G		intron_variant		3
MNAT1	ENST00000557134.1	c.389+24992A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41689 AN: 151758 Hom.: 6239 Cov.: 31

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.305

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.274 AC: 41670 AN: 151876 Hom.: 6231 Cov.: 31 AF XY: 0.271 AC XY: 20134 AN XY: 74248

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.306

Alfa AF: 0.271 Hom.: 881

Bravo AF: 0.268

Asia WGS AF: 0.346 AC: 1202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.30
DANN	Benign	0.53

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: rs4151330; hg19: chr14-61371545;