7-157005198-G-T

Position:

• chr7-157005198-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005515.4(MNX1):​c.*322C>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 0.00511 in 239,366 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0072 (17 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (2 hom.)
• Consequence: MNX1 NM_005515.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.31

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 7-157005198-G-T is Benign according to our data. Variant chr7-157005198-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1200101.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00723 (1100/152178) while in subpopulation AFR AF= 0.0249 (1032/41512). AF 95% confidence interval is 0.0236. There are 17 homozygotes in gnomad4. There are 513 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1100 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MNX1	NM_005515.4	c.*322C>A		3_prime_UTR_variant	3/3	ENST00000252971.11
MNX1	NM_001165255.2	c.*322C>A		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MNX1	ENST00000252971.11	c.*322C>A		3_prime_UTR_variant	3/3	1	NM_005515.4	P2
MNX1	ENST00000543409.5	c.*322C>A		3_prime_UTR_variant	3/3	1		A2
MNX1	ENST00000469500.5	c.55+3800C>A		intron_variant		1
MNX1	ENST00000479817.1	c.38+4462C>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.00723 AC: 1100 AN: 152060 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0249

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00621

GnomAD4 exome AF: 0.00141 AC: 123 AN: 87188 Hom.: 2 Cov.: 0 AF XY: 0.00148 AC XY: 61 AN XY: 41232

Gnomad4 AFR exome AF: 0.0231

Gnomad4 AMR exome AF: 0.000754

Gnomad4 ASJ exome AF: 0.00197

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000367

Gnomad4 OTH exome AF: 0.00299

GnomAD4 genome AF: 0.00723 AC: 1100 AN: 152178 Hom.: 17 Cov.: 32 AF XY: 0.00690 AC XY: 513 AN XY: 74400

Gnomad4 AFR AF: 0.0249

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.00399 Hom.: 3

Bravo AF: 0.00891

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely 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	-0.88
CADD	Benign	1.2
DANN	Benign	0.81
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

Publications

LitVar

Other links and lift over

dbSNP: rs116264913; hg19: chr7-156797892;