rs8012779

chr14-60964898-T-C

Variant summary

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

The NM_002431.4(MNAT1):c.810-3331T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 152,236 control chromosomes in the GnomAD database, including 63,790 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 0.91 (63790 hom., cov: 32)
• Consequence: MNAT1 NM_002431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209

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=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.98 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MNAT1	NM_002431.4	c.810-3331T>C		intron_variant		ENST00000261245.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MNAT1	ENST00000261245.9	c.810-3331T>C		intron_variant		1	NM_002431.4	P1
MNAT1	ENST00000539616.6	c.684-3331T>C		intron_variant		1
MNAT1	ENST00000554002.5	c.495-3661T>C		intron_variant		3
MNAT1	ENST00000557134.1	c.390-3331T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.911 AC: 138596 AN: 152118 Hom.: 63752 Cov.: 32

Gnomad AFR AF: 0.806

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.878

Gnomad ASJ AF: 0.948

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.990

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.986

Gnomad OTH AF: 0.917

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

GnomAD4 genome AF: 0.911 AC: 138692 AN: 152236 Hom.: 63790 Cov.: 32 AF XY: 0.907 AC XY: 67541 AN XY: 74438

Gnomad4 AFR AF: 0.806

Gnomad4 AMR AF: 0.878

Gnomad4 ASJ AF: 0.948

Gnomad4 EAS AF: 0.790

Gnomad4 SAS AF: 0.767

Gnomad4 FIN AF: 0.990

Gnomad4 NFE AF: 0.986

Gnomad4 OTH AF: 0.913

Alfa AF: 0.967 Hom.: 132164

Bravo AF: 0.901

Asia WGS AF: 0.771 AC: 2681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	3.4
Dann	Benign	0.62

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: rs8012779; hg19: chr14-61431616;