7-157006473-G-A

Variant names:

• chr7-157006473-G-A
• rs751908396
• NM_005515.4:c.852+6C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005515.4(MNX1):​c.852+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MNX1 NM_005515.4 splice_region, intron
• Scores: Splicing: ADA: 0.0002115
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.37
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005515.4. 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
	MNX1	NM_005515.4	MANE Select	c.852+6C>T		splice_region intron	N/A	NP_005506.3
	MNX1	NM_001165255.2		c.216+6C>T		splice_region intron	N/A	NP_001158727.1	P50219-2
	MNX1-AS2	NR_147077.1		n.118+49G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MNX1	ENST00000252971.11	TSL:1 MANE Select	c.852+6C>T		splice_region intron	N/A	ENSP00000252971.5	P50219-1
	MNX1	ENST00000543409.5	TSL:1	c.216+6C>T		splice_region intron	N/A	ENSP00000438552.1	P50219-2
	MNX1	ENST00000428439.1	TSL:1	c.216+6C>T		splice_region intron	N/A	ENSP00000401158.1	C9K088

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000416 AC: 1 AN: 240512 AF XY: 0.00000766

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000295

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456508 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724138

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.0000225 AC: 1 AN: 44400

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25908

East Asian (EAS) AF: 0.00 AC: 0 AN: 39602

South Asian (SAS) AF: 0.00 AC: 0 AN: 85166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51652

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5550

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110662

Other (OTH) AF: 0.00 AC: 0 AN: 60130

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	18
DANN	Benign	0.97
PhyloP100		2.4

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00021
dbscSNV1_RF	Benign	0.0060
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: rs751908396; hg19: chr7-156799167;