rs157705

Variant names:

• chr6-90515416-C-T
• rs157705
• NM_145331.3:c.*1085G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145331.3(MAP3K7):​c.*1085G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 151,652 control chromosomes in the GnomAD database, including 10,033 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 0.36 (10033 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: MAP3K7 NM_145331.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.906
• Publications: 11 publications found

Genes affected

MAP3K7 (HGNC:6859): (mitogen-activated protein kinase kinase kinase 7) The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase mediates the signaling transduction induced by TGF beta and morphogenetic protein (BMP), and controls a variety of cell functions including transcription regulation and apoptosis. In response to IL-1, this protein forms a kinase complex including TRAF6, MAP3K7P1/TAB1 and MAP3K7P2/TAB2; this complex is required for the activation of nuclear factor kappa B. This kinase can also activate MAPK8/JNK, MAP2K4/MKK4, and thus plays a role in the cell response to environmental stresses. Four alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

MAP3K7 Gene-Disease associations (from GenCC):

• cardiospondylocarpofacial syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• frontometaphyseal dysplasia

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Illumina
• frontometaphyseal dysplasia 2

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K7	NM_145331.3	c.*1085G>A		3_prime_UTR_variant	Exon 17 of 17	ENST00000369329.8	NP_663304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K7	ENST00000369329.8	c.*1085G>A		3_prime_UTR_variant	Exon 17 of 17	1	NM_145331.3	ENSP00000358335.3

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54134 AN: 151534 Hom.: 10024 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.380

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.357 AC: 54190 AN: 151652 Hom.: 10033 Cov.: 32 AF XY: 0.353 AC XY: 26168 AN XY: 74152

African (AFR) AF: 0.448 AC: 18550 AN: 41380

American (AMR) AF: 0.347 AC: 5275 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1621 AN: 3462

East Asian (EAS) AF: 0.316 AC: 1631 AN: 5158

South Asian (SAS) AF: 0.424 AC: 2041 AN: 4814

European-Finnish (FIN) AF: 0.239 AC: 2523 AN: 10548

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21314 AN: 67756

Other (OTH) AF: 0.385 AC: 813 AN: 2112

Alfa AF: 0.333 Hom.: 11765

Bravo AF: 0.365

Asia WGS AF: 0.355 AC: 1235 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.5
DANN	Benign	0.71
PhyloP100		0.91
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: rs157705; hg19: chr6-91225135;