chr14-70808878-C-T

Variant names:

• chr14-70808878-C-T
• rs773676020
• NM_001284230.2:c.294G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001284230.2(MAP3K9):​c.294G>A​(p.Gln98Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,447,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: MAP3K9 NM_001284230.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.28
• Publications: 0 publications found

Genes affected

MAP3K9 (HGNC:6861): (mitogen-activated protein kinase kinase kinase 9) Enables protein serine/threonine kinase activity. Involved in protein autophosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

MAP3K9-DT (HGNC:53189): (MAP3K9 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 14-70808878-C-T is Benign according to our data. Variant chr14-70808878-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2644347.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.28 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284230.2. 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
	MAP3K9	NM_001284230.2	MANE Select	c.294G>A	p.Gln98Gln	synonymous	Exon 1 of 12	NP_001271159.1	P80192-1
	MAP3K9	NM_033141.4		c.294G>A	p.Gln98Gln	synonymous	Exon 1 of 13	NP_149132.2
	MAP3K9-DT	NR_184163.1		n.95C>T		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K9	ENST00000554752.7	TSL:1 MANE Select	c.294G>A	p.Gln98Gln	synonymous	Exon 1 of 12	ENSP00000451612.2	P80192-1
	MAP3K9	ENST00000555993.6	TSL:1	c.294G>A	p.Gln98Gln	synonymous	Exon 1 of 13	ENSP00000451263.2	P80192-4
	MAP3K9	ENST00000933971.1		c.294G>A	p.Gln98Gln	synonymous	Exon 1 of 11	ENSP00000604030.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.0000136 AC: 3 AN: 220442 AF XY: 0.0000166

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000276 AC: 4 AN: 1447552 Hom.: 0 Cov.: 41 AF XY: 0.00000417 AC XY: 3 AN XY: 719260

African (AFR) AF: 0.00 AC: 0 AN: 33298

American (AMR) AF: 0.00 AC: 0 AN: 43172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25838

East Asian (EAS) AF: 0.00 AC: 0 AN: 39214

South Asian (SAS) AF: 0.0000476 AC: 4 AN: 83956

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108010

Other (OTH) AF: 0.00 AC: 0 AN: 59892

GnomAD4 genome Cov.: 29

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	14
DANN	Uncertain	0.97
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs773676020; hg19: chr14-71275595;