rs4151150

Positions:

• chr14-60734916-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_002431.4(MNAT1):​c.54C>T​(p.Ser18Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0161 in 1,614,102 control chromosomes in the GnomAD database, including 400 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 0.016 (40 hom., cov: 32)
  • Exomes 𝑓: 0.016 (360 hom.)
• Consequence: MNAT1 NM_002431.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP7: Synonymous conserved (PhyloP=-0.188 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MNAT1	NM_002431.4	c.54C>T	p.Ser18Ser	synonymous_variant	1/8	ENST00000261245.9	NP_002422.1
MNAT1	NM_001177963.2	c.54C>T	p.Ser18Ser	synonymous_variant	1/7		NP_001171434.1
MNAT1	XM_005267688.4	c.54C>T	p.Ser18Ser	synonymous_variant	1/8		XP_005267745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MNAT1	ENST00000261245.9	c.54C>T	p.Ser18Ser	synonymous_variant	1/8	1	NM_002431.4	ENSP00000261245.4

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2443 AN: 152126 Hom.: 40 Cov.: 32

Gnomad AFR AF: 0.0224

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0592

Gnomad FIN AF: 0.00688

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0127

Gnomad OTH AF: 0.0248

GnomAD3 exomes AF: 0.0176 AC: 4436 AN: 251470 Hom.: 91 AF XY: 0.0201 AC XY: 2728 AN XY: 135914

Gnomad AFR exome AF: 0.0213

Gnomad AMR exome AF: 0.00723

Gnomad ASJ exome AF: 0.0132

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.0627

Gnomad FIN exome AF: 0.00564

Gnomad NFE exome AF: 0.0138

Gnomad OTH exome AF: 0.0145

GnomAD4 exome AF: 0.0161 AC: 23503 AN: 1461858 Hom.: 360 Cov.: 30 AF XY: 0.0174 AC XY: 12638 AN XY: 727228

Gnomad4 AFR exome AF: 0.0232

Gnomad4 AMR exome AF: 0.00738

Gnomad4 ASJ exome AF: 0.0148

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.0631

Gnomad4 FIN exome AF: 0.00584

Gnomad4 NFE exome AF: 0.0134

Gnomad4 OTH exome AF: 0.0186

GnomAD4 genome AF: 0.0161 AC: 2444 AN: 152244 Hom.: 40 Cov.: 32 AF XY: 0.0166 AC XY: 1233 AN XY: 74442

Gnomad4 AFR AF: 0.0224

Gnomad4 AMR AF: 0.0106

Gnomad4 ASJ AF: 0.00980

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0594

Gnomad4 FIN AF: 0.00688

Gnomad4 NFE AF: 0.0127

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0151 Hom.: 20

Bravo AF: 0.0152

Asia WGS AF: 0.0250 AC: 87 AN: 3478

EpiCase AF: 0.0144

EpiControl AF: 0.0158

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	8.2
DANN	Benign	0.91

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: rs4151150; hg19: chr14-61201634;