rs4151182

Positions:

• chr14-60775032-A-C
• chr14-60775032-A-T

Variant summary

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

The NM_002431.4(MNAT1):​c.90-21185A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 151,906 control chromosomes in the GnomAD database, including 35,042 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 0.68 (35042 hom., cov: 30)
• Consequence: MNAT1 NM_002431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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]

MNAT1 (HGNC:):

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 (AMR) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MNAT1	NM_002431.4	c.90-21185A>C		intron_variant		ENST00000261245.9	NP_002422.1
MNAT1	NM_001177963.2	c.90-21185A>C		intron_variant			NP_001171434.1
MNAT1	XM_005267688.4	c.90-21185A>C		intron_variant			XP_005267745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MNAT1	ENST00000261245.9	c.90-21185A>C		intron_variant		1	NM_002431.4	ENSP00000261245.4
MNAT1	ENST00000539616.6	c.90-21185A>C		intron_variant		1		ENSP00000446437.2
MNAT1	ENST00000556764.5	n.180-21185A>C		intron_variant		1
MNAT1	ENST00000553354.5	n.174-33293A>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102559 AN: 151788 Hom.: 35042 Cov.: 30

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.675 AC: 102603 AN: 151906 Hom.: 35042 Cov.: 30 AF XY: 0.676 AC XY: 50169 AN XY: 74220

Gnomad4 AFR AF: 0.584

Gnomad4 AMR AF: 0.736

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.648

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.727

Gnomad4 NFE AF: 0.716

Gnomad4 OTH AF: 0.688

Alfa AF: 0.615 Hom.: 1850

Bravo AF: 0.675

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.65
DANN	Benign	0.67

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: rs4151182; hg19: chr14-61241750;