rs1114167350

Variant names:

• chr4-6054100-C-G
• rs1114167350
• NM_001099433.2:c.1756G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_001099433.2(JAKMIP1):​c.1756G>C​(p.Asp586His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. D586D) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: JAKMIP1 NM_001099433.2 missense
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 7.51
• Publications: 1 publications found

Genes affected

JAKMIP1 (HGNC:26460): (janus kinase and microtubule interacting protein 1) Enables GABA receptor binding activity and RNA binding activity. Involved in cognition. Is extrinsic component of membrane. Part of ribonucleoprotein complex. [provided by Alliance of Genome Resources, Apr 2022]

C4orf50 (HGNC:33766): (chromosome 4 open reading frame 50)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 4-6054100-C-G is Pathogenic according to our data. Variant chr4-6054100-C-G is described in ClinVar as Pathogenic. ClinVar VariationId is 254206.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099433.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAKMIP1	NM_001099433.2	MANE Select	c.1756G>C	p.Asp586His	missense	Exon 13 of 21	NP_001092903.1
	JAKMIP1	NM_001306133.2		c.1756G>C	p.Asp586His	missense	Exon 13 of 13	NP_001293062.1
	JAKMIP1	NM_144720.4		c.1756G>C	p.Asp586His	missense	Exon 13 of 13	NP_653321.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAKMIP1	ENST00000409021.9	TSL:1 MANE Select	c.1756G>C	p.Asp586His	missense	Exon 13 of 21	ENSP00000386711.3
	JAKMIP1	ENST00000409371.8	TSL:1	c.1201G>C	p.Asp401His	missense	Exon 11 of 19	ENSP00000387042.3
	JAKMIP1	ENST00000282924.9	TSL:1	c.1756G>C	p.Asp586His	missense	Exon 13 of 13	ENSP00000282924.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Smith-Magenis Syndrome-like (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	2.0	M
PhyloP100		7.5
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.016	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.12		Loss of helix (P = 0.2022)
MVP		0.46
MPC		1.8
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.78
gMVP		0.61
Mutation Taster		=0/100	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs1114167350; hg19: chr4-6055827;