NM_002382.5:c.*943G>C

Variant names:

• chr14-65075533-C-G
• rs111875569
• NM_002382.5:c.*943G>C

Variant summary

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

The NM_002382.5(MAX):​c.*943G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000219 in 912,968 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: MAX NM_002382.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.931
• Publications: 0 publications found

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: ClinGen, Orphanet
• pheochromocytoma

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• polydactyly-macrocephaly syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

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=-0.8).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAX	NM_002382.5	MANE Select	c.*943G>C		3_prime_UTR	Exon 5 of 5	NP_002373.3
	MAX	NM_001407094.1		c.*943G>C		3_prime_UTR	Exon 6 of 6	NP_001394023.1	P61244-1
	MAX	NM_001407095.1		c.*943G>C		3_prime_UTR	Exon 5 of 5	NP_001394024.1	P61244-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAX	ENST00000358664.9	TSL:1 MANE Select	c.*943G>C		3_prime_UTR	Exon 5 of 5	ENSP00000351490.4	P61244-1
	MAX	ENST00000358402.8	TSL:1	c.*943G>C		3_prime_UTR	Exon 4 of 4	ENSP00000351175.4	P61244-2
	MAX	ENST00000284165.10	TSL:1	c.*2270G>C		3_prime_UTR	Exon 4 of 4	ENSP00000284165.6	P61244-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000219 AC: 2 AN: 912968 Hom.: 0 Cov.: 32 AF XY: 0.00000237 AC XY: 1 AN XY: 421510

African (AFR) AF: 0.00 AC: 0 AN: 19574

American (AMR) AF: 0.00 AC: 0 AN: 3434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10214

East Asian (EAS) AF: 0.00 AC: 0 AN: 14816

South Asian (SAS) AF: 0.0000583 AC: 1 AN: 17154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 750

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2100

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 810974

Other (OTH) AF: 0.0000295 AC: 1 AN: 33952

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	14
DANN	Benign	0.72
PhyloP100		0.93

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs111875569; hg19: chr14-65542251;