chr6-90550397-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_145331.3(MAP3K7):​c.949+71A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 995,822 control chromosomes in the GnomAD database, including 56,817 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (9934 hom., cov: 31)
  • Exomes 𝑓: 0.33 (46883 hom.)
• Consequence: MAP3K7 NM_145331.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 6-90550397-T-C is Benign according to our data. Variant chr6-90550397-T-C is described in ClinVar as [Benign]. Clinvar id is 1183798.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.356 AC: 53974 AN: 151774 Hom.: 9922 Cov.: 31

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.376

GnomAD4 exome AF: 0.329 AC: 277887 AN: 843928 Hom.: 46883 AF XY: 0.333 AC XY: 145899 AN XY: 438450

African (AFR) AF: 0.459 AC: 9235 AN: 20134

American (AMR) AF: 0.296 AC: 8318 AN: 28144

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 8669 AN: 18910

East Asian (EAS) AF: 0.329 AC: 11694 AN: 35578

South Asian (SAS) AF: 0.419 AC: 25925 AN: 61934

European-Finnish (FIN) AF: 0.245 AC: 11571 AN: 47248

Middle Eastern (MID) AF: 0.415 AC: 1803 AN: 4340

European-Non Finnish (NFE) AF: 0.318 AC: 187253 AN: 588974

Other (OTH) AF: 0.347 AC: 13419 AN: 38666

GnomAD4 genome AF: 0.356 AC: 54042 AN: 151894 Hom.: 9934 Cov.: 31 AF XY: 0.352 AC XY: 26117 AN XY: 74276

African (AFR) AF: 0.445 AC: 18446 AN: 41408

American (AMR) AF: 0.342 AC: 5223 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1625 AN: 3468

East Asian (EAS) AF: 0.316 AC: 1634 AN: 5170

South Asian (SAS) AF: 0.423 AC: 2042 AN: 4824

European-Finnish (FIN) AF: 0.239 AC: 2523 AN: 10566

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.315 AC: 21358 AN: 67898

Other (OTH) AF: 0.381 AC: 803 AN: 2108

Alfa AF: 0.345 Hom.: 2633

Bravo AF: 0.363

Asia WGS AF: 0.357 AC: 1243 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Benign	0.87
PhyloP100		0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs205343; hg19: chr6-91260116; COSMIC: COSV65223762;