6-90550397-T-A

Variant names:

• chr6-90550397-T-A
• rs205343
• NM_145331.3:c.949+71A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145331.3(MAP3K7):​c.949+71A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAP3K7 NM_145331.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.575
• Publications: 5 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K7	NM_145331.3	c.949+71A>T		intron_variant	Intron 9 of 16	ENST00000369329.8	NP_663304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K7	ENST00000369329.8	c.949+71A>T		intron_variant	Intron 9 of 16	1	NM_145331.3	ENSP00000358335.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 846454 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 439746

African (AFR) AF: 0.00 AC: 0 AN: 20206

American (AMR) AF: 0.00 AC: 0 AN: 28206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18976

East Asian (EAS) AF: 0.00 AC: 0 AN: 35638

South Asian (SAS) AF: 0.00 AC: 0 AN: 62132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4346

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 590876

Other (OTH) AF: 0.00 AC: 0 AN: 38740

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Benign	0.84
PhyloP100		0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs205343; hg19: chr6-91260116;