Genetic Variant NM_020184.4:c.82_90dupGTGCTGCTG (chr2-96761070-C-CGGTGCTGCT) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is . The variant received 4 ACMG points: 4P and 0B. PM2PM4

The NM_020184.4(CNNM4):c.82_90dupGTGCTGCTG(p.Val28_Leu30dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000442 in 1,131,472 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

CNNM4
NM_020184.4 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.01

Publications

0 publications found

Variant links:

Genes affected

CNNM4 (HGNC:105): (cyclin and CBS domain divalent metal cation transport mediator 4) This gene encodes a member of the ancient conserved domain containing protein family. Members of this protein family contain a cyclin box motif and have structural similarity to the cyclins. The encoded protein may play a role in metal ion transport. Mutations in this gene are associated with Jalili syndrome which consists of cone-rod dystrophy and amelogenesis imperfecta. [provided by RefSeq, Feb 2010]

CNNM4 Gene-Disease associations (from GenCC):

Jalili syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics

CNNM4 links:

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new If you want to explore the variant's impact on the transcript NM_020184.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_020184.4.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020184.4. 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
	CNNM4	NM_020184.4	MANE Select	c.82_90dupGTGCTGCTG	p.Val28_Leu30dup	conservative_inframe_insertion	Exon 1 of 7	NP_064569.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNNM4	ENST00000377075.3	TSL:1 MANE Select	c.82_90dupGTGCTGCTG	p.Val28_Leu30dup	conservative_inframe_insertion	Exon 1 of 7	ENSP00000366275.2	Q6P4Q7-1
CNNM4	ENST00000930282.1		c.82_90dupGTGCTGCTG	p.Val28_Leu30dup	conservative_inframe_insertion	Exon 1 of 7	ENSP00000600341.1
CNNM4	ENST00000966765.1		c.82_90dupGTGCTGCTG	p.Val28_Leu30dup	conservative_inframe_insertion	Exon 1 of 8	ENSP00000636824.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

57252

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000442

AC:

AN:

1131472

Hom.:

Cov.:

AF XY:

0.00000556

AC XY:

AN XY:

539420

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24240

American (AMR)

AF:

0.00

AC:

AN:

11484

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14860

East Asian (EAS)

AF:

0.00

AC:

AN:

28772

South Asian (SAS)

AF:

0.00

AC:

AN:

24566

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34738

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4276

European-Non Finnish (NFE)

AF:

0.00000530

AC:

AN:

943130

Other (OTH)

AF:

0.00

AC:

AN:

45406

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.0

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over