rs1171352404

Variant names:

• chr2-96761033-G-A
• NM_020184.4:c.34G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-96761033-G-A
• chr2-96761033-G-C
• chr2-96761033-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020184.4(CNNM4):​c.34G>A​(p.Gly12Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000281 in 1,066,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: CNNM4 NM_020184.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25377756).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNNM4	NM_020184.4	c.34G>A	p.Gly12Ser	missense_variant	Exon 1 of 7	ENST00000377075.3	NP_064569.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNNM4	ENST00000377075.3	c.34G>A	p.Gly12Ser	missense_variant	Exon 1 of 7	1	NM_020184.4	ENSP00000366275.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000281 AC: 3 AN: 1066032 Hom.: 0 Cov.: 31 AF XY: 0.00000199 AC XY: 1 AN XY: 503418

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000330

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	16
DANN	Benign	0.86
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.41	T
M_CAP	Pathogenic	0.78	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.7	L
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.099
Sift	Benign	0.46	T
Sift4G	Benign	0.22	T
Polyphen		0.0020	B
Vest4		0.23
MutPred		0.25		Gain of glycosylation at G12 (P = 0.004);
MVP		0.63
MPC		1.0
ClinPred		0.18	T
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.081
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-97426770;