7-157005607-G-A

Position:

• chr7-157005607-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_005515.4(MNX1):​c.1119C>T​(p.Gly373=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,452,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: MNX1 NM_005515.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0610

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 7-157005607-G-A is Benign according to our data. Variant chr7-157005607-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2973084.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.061 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MNX1	NM_005515.4	c.1119C>T	p.Gly373=	synonymous_variant	3/3	ENST00000252971.11	NP_005506.3
MNX1	NM_001165255.2	c.483C>T	p.Gly161=	synonymous_variant	3/3		NP_001158727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MNX1	ENST00000252971.11	c.1119C>T	p.Gly373=	synonymous_variant	3/3	1	NM_005515.4	ENSP00000252971	P2
MNX1	ENST00000543409.5	c.483C>T	p.Gly161=	synonymous_variant	3/3	1		ENSP00000438552	A2
MNX1	ENST00000469500.5	c.55+3391C>T		intron_variant		1		ENSP00000475129
MNX1	ENST00000479817.1	c.38+4053C>T		intron_variant		1		ENSP00000474286

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000413 AC: 6 AN: 1452750 Hom.: 0 Cov.: 31 AF XY: 0.00000692 AC XY: 5 AN XY: 722292

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.0000235

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000468 Hom.: 0

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

Labcorp Genetics (formerly Invitae), Labcorp

Aug 05, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.5
DANN	Benign	0.96

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: rs772480927; hg19: chr7-156798301; COSMIC: COSV53319536; COSMIC: COSV53319536;