chr14-60775032-A-C

Variant names:

• chr14-60775032-A-C
• rs4151182
• NM_002431.4:c.90-21185A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MNAT1	NM_002431.4	c.90-21185A>C		intron_variant	Intron 1 of 7	ENST00000261245.9	NP_002422.1
MNAT1	NM_001177963.2	c.90-21185A>C		intron_variant	Intron 1 of 6		NP_001171434.1
MNAT1	XM_005267688.4	c.90-21185A>C		intron_variant	Intron 1 of 7		XP_005267745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MNAT1	ENST00000261245.9	c.90-21185A>C		intron_variant	Intron 1 of 7	1	NM_002431.4	ENSP00000261245.4
MNAT1	ENST00000539616.6	c.90-21185A>C		intron_variant	Intron 1 of 6	1		ENSP00000446437.2
MNAT1	ENST00000556764.5	n.180-21185A>C		intron_variant	Intron 1 of 3	1
MNAT1	ENST00000553354.5	n.174-33293A>C		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.584 AC: 24145 AN: 41376

American (AMR) AF: 0.736 AC: 11232 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2109 AN: 3468

East Asian (EAS) AF: 0.648 AC: 3340 AN: 5152

South Asian (SAS) AF: 0.648 AC: 3111 AN: 4800

European-Finnish (FIN) AF: 0.727 AC: 7669 AN: 10554

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.716 AC: 48679 AN: 67982

Other (OTH) AF: 0.688 AC: 1448 AN: 2104

Alfa AF: 0.671 Hom.: 7929

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
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4151182; hg19: chr14-61241750;