rs113043441

Variant names:

• chr14-60796349-C-T
• rs113043441
• NM_002431.4:c.222C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_002431.4(MNAT1):​c.222C>T​(p.Ile74Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000637 in 1,611,472 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00048 (2 hom.)
• Consequence: MNAT1 NM_002431.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.586
• Publications: 1 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 14-60796349-C-T is Benign according to our data. Variant chr14-60796349-C-T is described in ClinVar as Benign. ClinVar VariationId is 790144.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.586 with no splicing effect.
• BS2: High AC in GnomAd4 at 329 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002431.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MNAT1	NM_002431.4	MANE Select	c.222C>T	p.Ile74Ile	synonymous	Exon 2 of 8	NP_002422.1	A0A024R688
	MNAT1	NM_001177963.2		c.222C>T	p.Ile74Ile	synonymous	Exon 2 of 7	NP_001171434.1	P51948-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MNAT1	ENST00000261245.9	TSL:1 MANE Select	c.222C>T	p.Ile74Ile	synonymous	Exon 2 of 8	ENSP00000261245.4	P51948-1
	MNAT1	ENST00000539616.6	TSL:1	c.222C>T	p.Ile74Ile	synonymous	Exon 2 of 7	ENSP00000446437.2	P51948-2
	MNAT1	ENST00000556764.5	TSL:1	n.312C>T		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes AF: 0.00216 AC: 328 AN: 152096 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00534

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.000852 AC: 212 AN: 248870 AF XY: 0.000736

Gnomad AFR exome AF: 0.00532

Gnomad AMR exome AF: 0.00147

Gnomad ASJ exome AF: 0.00200

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000390

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.000478 AC: 698 AN: 1459258 Hom.: 2 Cov.: 30 AF XY: 0.000468 AC XY: 340 AN XY: 725876

African (AFR) AF: 0.00574 AC: 191 AN: 33260

American (AMR) AF: 0.00163 AC: 72 AN: 44230

Ashkenazi Jewish (ASJ) AF: 0.00169 AC: 44 AN: 26038

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.000117 AC: 10 AN: 85668

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00365 AC: 21 AN: 5746

European-Non Finnish (NFE) AF: 0.000265 AC: 294 AN: 1111002

Other (OTH) AF: 0.00109 AC: 66 AN: 60288

GnomAD4 genome AF: 0.00216 AC: 329 AN: 152214 Hom.: 0 Cov.: 32 AF XY: 0.00198 AC XY: 147 AN XY: 74426

African (AFR) AF: 0.00534 AC: 222 AN: 41540

American (AMR) AF: 0.00393 AC: 60 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68012

Other (OTH) AF: 0.00664 AC: 14 AN: 2110

Alfa AF: 0.00146 Hom.: 0

Bravo AF: 0.00267

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000383

EpiControl AF: 0.000476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	12
DANN	Benign	0.70
PhyloP100		0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs113043441; hg19: chr14-61263067; COSMIC: COSV106394018;