rs139403325

Variant names:

• chr14-65075776-C-A
• rs139403325
• NM_002382.5:c.*700G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-65075776-C-A
• chr14-65075776-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002382.5(MAX):​c.*700G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,066,602 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00089 (3 hom.)
• Consequence: MAX NM_002382.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.401
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 14-65075776-C-A is Benign according to our data. Variant chr14-65075776-C-A is described in ClinVar as Benign. ClinVar VariationId is 880681.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00241 (367/152272) while in subpopulation AFR AF = 0.00705 (293/41554). AF 95% confidence interval is 0.00639. There are 1 homozygotes in GnomAd4. There are 165 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 367 AD gene.

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.*700G>T		3_prime_UTR	Exon 5 of 5	NP_002373.3
	MAX	NM_001407094.1		c.*700G>T		3_prime_UTR	Exon 6 of 6	NP_001394023.1	P61244-1
	MAX	NM_001407095.1		c.*700G>T		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.*700G>T		3_prime_UTR	Exon 5 of 5	ENSP00000351490.4	P61244-1
	MAX	ENST00000358402.8	TSL:1	c.*700G>T		3_prime_UTR	Exon 4 of 4	ENSP00000351175.4	P61244-2
	MAX	ENST00000284165.10	TSL:1	c.*2027G>T		3_prime_UTR	Exon 4 of 4	ENSP00000284165.6	P61244-4

Frequencies

GnomAD3 genomes AF: 0.00241 AC: 367 AN: 152154 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00707

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000472

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.000895 AC: 818 AN: 914330 Hom.: 3 Cov.: 33 AF XY: 0.000815 AC XY: 344 AN XY: 422134

African (AFR) AF: 0.00835 AC: 164 AN: 19636

American (AMR) AF: 0.00113 AC: 4 AN: 3528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10236

East Asian (EAS) AF: 0.00 AC: 0 AN: 14956

South Asian (SAS) AF: 0.00 AC: 0 AN: 17200

European-Finnish (FIN) AF: 0.00152 AC: 1 AN: 656

Middle Eastern (MID) AF: 0.000947 AC: 2 AN: 2112

European-Non Finnish (NFE) AF: 0.000752 AC: 611 AN: 811984

Other (OTH) AF: 0.00106 AC: 36 AN: 34022

GnomAD4 genome AF: 0.00241 AC: 367 AN: 152272 Hom.: 1 Cov.: 33 AF XY: 0.00222 AC XY: 165 AN XY: 74450

African (AFR) AF: 0.00705 AC: 293 AN: 41554

American (AMR) AF: 0.000327 AC: 5 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000472 AC: 5 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000897 AC: 61 AN: 68018

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00107 Hom.: 0

Bravo AF: 0.00262

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Pheochromocytoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.1
DANN	Benign	0.58
PhyloP100		0.40
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: rs139403325; hg19: chr14-65542494;