7-157006387-T-C

Position:

• chr7-157006387-T-C

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.852+92A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,412,262 control chromosomes in the GnomAD database, including 18,096 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (6325 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11771 hom.)
• Consequence: MNX1 NM_005515.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.19

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]

MNX1-AS2 (HGNC:40278): (MNX1 antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 7-157006387-T-C is Benign according to our data. Variant chr7-157006387-T-C is described in ClinVar as [Benign]. Clinvar id is 1237122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MNX1	NM_005515.4	c.852+92A>G		intron_variant		ENST00000252971.11	NP_005506.3
MNX1-AS2	NR_147077.1	n.81T>C		non_coding_transcript_exon_variant	1/2
MNX1	NM_001165255.2	c.216+92A>G		intron_variant			NP_001158727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MNX1	ENST00000252971.11	c.852+92A>G		intron_variant		1	NM_005515.4	ENSP00000252971	P2
MNX1-AS2	ENST00000429228.1	n.81T>C		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34040 AN: 151874 Hom.: 6308 Cov.: 32

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.0911

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.0698

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0993

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.117 AC: 146891 AN: 1260270 Hom.: 11771 Cov.: 19 AF XY: 0.117 AC XY: 72583 AN XY: 620772

Gnomad4 AFR exome AF: 0.529

Gnomad4 AMR exome AF: 0.172

Gnomad4 ASJ exome AF: 0.0978

Gnomad4 EAS exome AF: 0.121

Gnomad4 SAS exome AF: 0.184

Gnomad4 FIN exome AF: 0.0765

Gnomad4 NFE exome AF: 0.0983

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.224 AC: 34095 AN: 151992 Hom.: 6325 Cov.: 32 AF XY: 0.222 AC XY: 16531 AN XY: 74310

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.0911

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.0698

Gnomad4 NFE AF: 0.0994

Gnomad4 OTH AF: 0.203

Alfa AF: 0.122 Hom.: 1614

Bravo AF: 0.245

Asia WGS AF: 0.184 AC: 639 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	-0.92
CADD	Benign	6.7
DANN	Benign	0.69

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: rs2270210; hg19: chr7-156799081;