NM_000245.4:c.*2240G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000245.4(MET):c.*2240G>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 0.37 in 187,378 control chromosomes in the GnomAD database, including 14,814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 11175 hom., cov: 32)

Exomes 𝑓: 0.45 ( 3639 hom. )

Consequence

MET
NM_000245.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.505

Publications

13 publications found

Variant links:

Genes affected

MET (HGNC:7029): (MET proto-oncogene, receptor tyrosine kinase) This gene encodes a member of the receptor tyrosine kinase family of proteins and the product of the proto-oncogene MET. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that are linked via disulfide bonds to form the mature receptor. Further processing of the beta subunit results in the formation of the M10 peptide, which has been shown to reduce lung fibrosis. Binding of its ligand, hepatocyte growth factor, induces dimerization and activation of the receptor, which plays a role in cellular survival, embryogenesis, and cellular migration and invasion. Mutations in this gene are associated with papillary renal cell carcinoma, hepatocellular carcinoma, and various head and neck cancers. Amplification and overexpression of this gene are also associated with multiple human cancers. [provided by RefSeq, May 2016]

MET Gene-Disease associations (from GenCC):

hereditary papillary renal cell carcinoma
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
papillary renal cell carcinoma
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, ClinGen
autosomal recessive nonsyndromic hearing loss 97
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
osteofibrous dysplasia
Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
arthrogryposis, distal, IIa 11
Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
nonsyndromic genetic hearing loss
Inheritance: AR Classification: LIMITED Submitted by: ClinGen
complex neurodevelopmental disorder
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

MET links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 7-116798364-G-A is Benign according to our data. Variant chr7-116798364-G-A is described in ClinVar as Benign. ClinVar VariationId is 358730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000245.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MET	NM_000245.4	MANE Select	c.*2240G>A	3_prime_UTR	Exon 21 of 21	NP_000236.2
MET	NM_001127500.3		c.*2240G>A	3_prime_UTR	Exon 21 of 21	NP_001120972.1	P08581-2
MET	NM_001324402.2		c.*2240G>A	3_prime_UTR	Exon 20 of 20	NP_001311331.1	B4DLF5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MET	ENST00000397752.8	TSL:1 MANE Select	c.*2240G>A	3_prime_UTR	Exon 21 of 21	ENSP00000380860.3	P08581-1
MET	ENST00000318493.11	TSL:1	c.*2240G>A	3_prime_UTR	Exon 21 of 21	ENSP00000317272.6	P08581-2
MET	ENST00000436117.3	TSL:1	n.*4018G>A	non_coding_transcript_exon	Exon 20 of 20	ENSP00000410980.2	P08581-3

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53445

AN:

151974

Hom.:

11188

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.307

Gnomad AMR

AF:

0.445

Gnomad ASJ

AF:

0.487

Gnomad EAS

AF:

0.471

Gnomad SAS

AF:

0.457

Gnomad FIN

AF:

0.383

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.451

Gnomad OTH

AF:

0.393

GnomAD4 exome

AF:

0.450

AC:

15879

AN:

35286

Hom.:

3639

Cov.:

AF XY:

0.456

AC XY:

7452

AN XY:

16352

show subpopulations

African (AFR)

AF:

0.0989

AC:

128

AN:

1294

American (AMR)

AF:

0.470

AC:

391

AN:

832

Ashkenazi Jewish (ASJ)

AF:

0.501

AC:

1095

AN:

2186

East Asian (EAS)

AF:

0.509

AC:

3265

AN:

6416

South Asian (SAS)

AF:

0.472

AC:

134

AN:

284

European-Finnish (FIN)

AF:

0.401

AC:

179

AN:

446

Middle Eastern (MID)

AF:

0.399

AC:

AN:

228

European-Non Finnish (NFE)

AF:

0.454

AC:

9415

AN:

20732

Other (OTH)

AF:

0.412

AC:

1181

AN:

2868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

427

854

1280

1707

2134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.351

AC:

53419

AN:

152092

Hom.:

11175

Cov.:

AF XY:

0.353

AC XY:

26275

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.105

AC:

4373

AN:

41526

American (AMR)

AF:

0.445

AC:

6790

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.487

AC:

1687

AN:

3464

East Asian (EAS)

AF:

0.471

AC:

2435

AN:

5170

South Asian (SAS)

AF:

0.455

AC:

2194

AN:

4818

European-Finnish (FIN)

AF:

0.383

AC:

4040

AN:

10562

Middle Eastern (MID)

AF:

0.412

AC:

121

AN:

294

European-Non Finnish (NFE)

AF:

0.451

AC:

30680

AN:

67960

Other (OTH)

AF:

0.388

AC:

819

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1612

3225

4837

6450

8062

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

524

1048

1572

2096

2620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.424

Hom.:

19172

Bravo

AF:

0.346

Asia WGS

AF:

0.415

AC:

1442

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Papillary renal cell carcinoma type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

0.51

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over