4-6029725-C-T

Variant names:

• chr4-6029725-C-T
• rs752154686
• NM_001099433.2:c.2436G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_001099433.2(JAKMIP1):​c.2436G>A​(p.Leu812Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000207 in 1,448,738 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: 0.000021 (0 hom.)
• Consequence: JAKMIP1 NM_001099433.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.816
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.13).
• BP6: Variant 4-6029725-C-T is Benign according to our data. Variant chr4-6029725-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 737928.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.816 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAKMIP1	NM_001099433.2	MANE Select	c.2436G>A	p.Leu812Leu	synonymous	Exon 20 of 21	NP_001092903.1	Q96N16-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAKMIP1	ENST00000409021.9	TSL:1 MANE Select	c.2436G>A	p.Leu812Leu	synonymous	Exon 20 of 21	ENSP00000386711.3	Q96N16-2
	JAKMIP1	ENST00000409371.8	TSL:1	c.1881G>A	p.Leu627Leu	synonymous	Exon 18 of 19	ENSP00000387042.3	Q96N16-5
	JAKMIP1	ENST00000637373.2	TSL:5	c.1140G>A	p.Leu380Leu	synonymous	Exon 13 of 14	ENSP00000490067.1	A0A1B0GUE0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.000121 AC: 28 AN: 231298 AF XY: 0.0000561

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000856

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: 0.0000207 AC: 30 AN: 1448738 Hom.: 0 Cov.: 29 AF XY: 0.00000973 AC XY: 7 AN XY: 719296

African (AFR) AF: 0.00 AC: 0 AN: 33346

American (AMR) AF: 0.000671 AC: 29 AN: 43232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25860

East Asian (EAS) AF: 0.00 AC: 0 AN: 39460

South Asian (SAS) AF: 0.00 AC: 0 AN: 83362

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52802

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1104932

Other (OTH) AF: 0.00 AC: 0 AN: 59998

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000491

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	7.4
DANN	Benign	0.79
PhyloP100		-0.82

Splicing

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

Other links and lift over

dbSNP: rs752154686; hg19: chr4-6031452;