Genetic Variant NM_002382.5:c.277G>T (chr14-65077931-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002382.5(MAX):c.277G>T(p.Ala93Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A93T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

MAX
NM_002382.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.13

Publications

0 publications found

Variant links:

Genes affected

MAX (HGNC:6913): (MYC associated factor X) The protein encoded by this gene is a member of the basic helix-loop-helix leucine zipper (bHLHZ) family of transcription factors. It is able to form homodimers and heterodimers with other family members, which include Mad, Mxi1 and Myc. Myc is an oncoprotein implicated in cell proliferation, differentiation and apoptosis. The homodimers and heterodimers compete for a common DNA target site (the E box) and rearrangement among these dimer forms provides a complex system of transcriptional regulation. Mutations of this gene have been reported to be associated with hereditary pheochromocytoma. A pseudogene of this gene is located on the long arm of chromosome 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

MAX Gene-Disease associations (from GenCC):

hereditary pheochromocytoma-paraganglioma
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
pheochromocytoma
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
polydactyly-macrocephaly syndrome
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

MAX links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002382.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MAX	NM_002382.5	MANE Select	c.277G>T	p.Ala93Ser	missense	Exon 4 of 5	NP_002373.3
MAX	NM_001320415.2		c.3G>T	p.Met1?	start_lost	Exon 4 of 6	NP_001307344.1
MAX	NM_001407105.1		c.3G>T	p.Met1?	start_lost	Exon 4 of 6	NP_001394034.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MAX	ENST00000358664.9	TSL:1 MANE Select	c.277G>T	p.Ala93Ser	missense	Exon 4 of 5	ENSP00000351490.4
MAX	ENST00000358402.8	TSL:1	c.250G>T	p.Ala84Ser	missense	Exon 3 of 4	ENSP00000351175.4
MAX	ENST00000284165.10	TSL:1	c.277G>T	p.Ala93Ser	missense	Exon 4 of 4	ENSP00000284165.6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.030

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.44

MetaRNN

Uncertain

0.45

MetaSVM

Uncertain

-0.18

MutationAssessor

Benign

1.6

PhyloP100

6.1

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.080

REVEL

Uncertain

0.45

Sift

Benign

0.56

Sift4G

Benign

0.79

Polyphen

0.054

Vest4

0.55

MutPred

0.40

Gain of phosphorylation at A93 (P = 0.032)

MVP

0.73

MPC

0.93

ClinPred

0.71

GERP RS

5.0

Varity_R

0.38

gMVP

0.66

Mutation Taster

=63/137

disease causing

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over