rs2225199

Positions:

• chr14-60905092-G-A
• chr14-60905092-G-T

Variant summary

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

The ENST00000261245.9(MNAT1):​c.809+25257G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.924 in 151,364 control chromosomes in the GnomAD database, including 65,190 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 0.92 (65190 hom., cov: 27)
• Consequence: MNAT1 ENST00000261245.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MNAT1	NM_002431.4	c.809+25257G>A		intron_variant		ENST00000261245.9	NP_002422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MNAT1	ENST00000261245.9	c.809+25257G>A		intron_variant		1	NM_002431.4	ENSP00000261245	P1
MNAT1	ENST00000539616.6	c.683+25257G>A		intron_variant		1		ENSP00000446437
MNAT1	ENST00000554002.5	c.494+25257G>A		intron_variant		3		ENSP00000451379
MNAT1	ENST00000557134.1	c.389+25257G>A		intron_variant		3		ENSP00000451017

Frequencies

GnomAD3 genomes AF: 0.924 AC: 139819 AN: 151246 Hom.: 65158 Cov.: 27

Gnomad AFR AF: 0.801

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.947

Gnomad ASJ AF: 0.952

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.993

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.992

Gnomad OTH AF: 0.934

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

GnomAD4 genome AF: 0.924 AC: 139909 AN: 151364 Hom.: 65190 Cov.: 27 AF XY: 0.923 AC XY: 68278 AN XY: 73956

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.947

Gnomad4 ASJ AF: 0.952

Gnomad4 EAS AF: 0.816

Gnomad4 SAS AF: 0.877

Gnomad4 FIN AF: 0.993

Gnomad4 NFE AF: 0.992

Gnomad4 OTH AF: 0.931

Alfa AF: 0.977 Hom.: 116822

Bravo AF: 0.918

Asia WGS AF: 0.851 AC: 2959 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.7
DANN	Benign	0.40

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: rs2225199; hg19: chr14-61371810;