NM_003010.4:c.*728dupG

Variant names:

• chr17-12141985-T-TG
• rs28921114
• NM_003010.4:c.*728dupG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_003010.4(MAP2K4):​c.*728dupG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0208 in 233,360 control chromosomes in the GnomAD database, including 59 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.021 (36 hom., cov: 32)
  • Exomes 𝑓: 0.021 (23 hom.)
• Consequence: MAP2K4 NM_003010.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• Publications: 1 publications found

Genes affected

MAP2K4 (HGNC:6844): (mitogen-activated protein kinase kinase 4) This gene encodes a member of the mitogen-activated protein kinase (MAPK) family. Members of this family act as an integration point for multiple biochemical signals and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation, and development. They form a three-tiered signaling module composed of MAPKKKs, MAPKKs, and MAPKs. This protein is phosphorylated at serine and threonine residues by MAPKKKs and subsequently phosphorylates downstream MAPK targets at threonine and tyrosine residues. A similar protein in mouse has been reported to play a role in liver organogenesis. A pseudogene of this gene is located on the long arm of chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0541 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003010.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K4	NM_003010.4	MANE Select	c.*728dupG		3_prime_UTR	Exon 11 of 11	NP_003001.1
	MAP2K4	NM_001281435.2		c.*728dupG		3_prime_UTR	Exon 12 of 12	NP_001268364.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K4	ENST00000353533.10	TSL:1 MANE Select	c.*728dupG		3_prime_UTR	Exon 11 of 11	ENSP00000262445.5
	MAP2K4	ENST00000536413.2	TSL:2	n.2110dupG		non_coding_transcript_exon	Exon 4 of 4
	MAP2K4	ENST00000415385.7	TSL:2	c.*728dupG		3_prime_UTR	Exon 12 of 12	ENSP00000410402.3

Frequencies

GnomAD3 genomes AF: 0.0205 AC: 3125 AN: 152162 Hom.: 36 Cov.: 32

Gnomad AFR AF: 0.0271

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0125

Gnomad ASJ AF: 0.00864

Gnomad EAS AF: 0.0595

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.0253

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0159

Gnomad OTH AF: 0.0167

GnomAD4 exome AF: 0.0212 AC: 1716 AN: 81080 Hom.: 23 Cov.: 0 AF XY: 0.0202 AC XY: 754 AN XY: 37314

African (AFR) AF: 0.0261 AC: 101 AN: 3876

American (AMR) AF: 0.0108 AC: 27 AN: 2490

Ashkenazi Jewish (ASJ) AF: 0.00785 AC: 40 AN: 5096

East Asian (EAS) AF: 0.0617 AC: 702 AN: 11380

South Asian (SAS) AF: 0.00143 AC: 1 AN: 700

European-Finnish (FIN) AF: 0.0216 AC: 10 AN: 462

Middle Eastern (MID) AF: 0.00816 AC: 4 AN: 490

European-Non Finnish (NFE) AF: 0.0144 AC: 716 AN: 49844

Other (OTH) AF: 0.0171 AC: 115 AN: 6742

GnomAD4 genome AF: 0.0206 AC: 3132 AN: 152280 Hom.: 36 Cov.: 32 AF XY: 0.0209 AC XY: 1556 AN XY: 74468

African (AFR) AF: 0.0272 AC: 1129 AN: 41554

American (AMR) AF: 0.0125 AC: 191 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00864 AC: 30 AN: 3472

East Asian (EAS) AF: 0.0596 AC: 309 AN: 5184

South Asian (SAS) AF: 0.00393 AC: 19 AN: 4830

European-Finnish (FIN) AF: 0.0253 AC: 268 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0159 AC: 1081 AN: 68020

Other (OTH) AF: 0.0166 AC: 35 AN: 2114

Alfa AF: 0.0153 Hom.: 4

Bravo AF: 0.0219

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5
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: rs28921114; hg19: chr17-12045302;