7-157005288-C-T

Position:

• chr7-157005288-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005515.4(MNX1):​c.*232G>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 0.107 in 279,522 control chromosomes in the GnomAD database, including 2,121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1531 hom., cov: 32)
  • Exomes 𝑓: 0.084 (590 hom.)
• Consequence: MNX1 NM_005515.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0750

Genes affected

MNX1 (HGNC:4979): (motor neuron and pancreas homeobox 1) This gene encodes a nuclear protein, which contains a homeobox domain and is a transcription factor. Mutations in this gene result in Currarino syndrome, an autosomic dominant congenital malformation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-157005288-C-T is Benign according to our data. Variant chr7-157005288-C-T is described in ClinVar as [Benign]. Clinvar id is 1259074.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MNX1	NM_005515.4	c.*232G>A		3_prime_UTR_variant	3/3	ENST00000252971.11
MNX1	NM_001165255.2	c.*232G>A		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MNX1	ENST00000252971.11	c.*232G>A		3_prime_UTR_variant	3/3	1	NM_005515.4	P2
MNX1	ENST00000543409.5	c.*232G>A		3_prime_UTR_variant	3/3	1		A2
MNX1	ENST00000469500.5	c.55+3710G>A		intron_variant		1
MNX1	ENST00000479817.1	c.38+4372G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19204 AN: 152142 Hom.: 1524 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0767

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0348

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.0918

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.0841 AC: 10699 AN: 127262 Hom.: 590 Cov.: 2 AF XY: 0.0824 AC XY: 5229 AN XY: 63482

Gnomad4 AFR exome AF: 0.209

Gnomad4 AMR exome AF: 0.121

Gnomad4 ASJ exome AF: 0.0822

Gnomad4 EAS exome AF: 0.0000776

Gnomad4 SAS exome AF: 0.0342

Gnomad4 FIN exome AF: 0.0687

Gnomad4 NFE exome AF: 0.0884

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.126 AC: 19235 AN: 152260 Hom.: 1531 Cov.: 32 AF XY: 0.123 AC XY: 9171 AN XY: 74440

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.0767

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0346

Gnomad4 FIN AF: 0.0649

Gnomad4 NFE AF: 0.0918

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0653 Hom.: 87

Bravo AF: 0.136

Asia WGS AF: 0.0320 AC: 114 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.91

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

LitVar

Other links and lift over

dbSNP: rs66587043; hg19: chr7-156797982;