4-6036057-C-T

Variant names:

• chr4-6036057-C-T
• rs146662557
• NM_001099433.2:c.2226G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001099433.2(JAKMIP1):​c.2226G>A​(p.Pro742Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,557,330 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00059 (6 hom.)
• Consequence: JAKMIP1 NM_001099433.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.85
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-6036057-C-T is Benign according to our data. Variant chr4-6036057-C-T is described in ClinVar as Benign. ClinVar VariationId is 714239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.85 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0051 (777/152388) while in subpopulation AFR AF = 0.0166 (691/41604). AF 95% confidence interval is 0.0156. There are 4 homozygotes in GnomAd4. There are 351 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 gene

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.2226G>A	p.Pro742Pro	synonymous	Exon 19 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.2226G>A	p.Pro742Pro	synonymous	Exon 19 of 21	ENSP00000386711.3	Q96N16-2
	JAKMIP1	ENST00000409371.8	TSL:1	c.1671G>A	p.Pro557Pro	synonymous	Exon 17 of 19	ENSP00000387042.3	Q96N16-5
	JAKMIP1	ENST00000637373.2	TSL:5	c.930G>A	p.Pro310Pro	synonymous	Exon 12 of 14	ENSP00000490067.1	A0A1B0GUE0

Frequencies

GnomAD3 genomes AF: 0.00508 AC: 774 AN: 152270 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0166

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00138 AC: 224 AN: 162812 AF XY: 0.00121

Gnomad AFR exome AF: 0.0193

Gnomad AMR exome AF: 0.000989

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00157

Gnomad NFE exome AF: 0.0000769

Gnomad OTH exome AF: 0.000440

GnomAD4 exome AF: 0.000590 AC: 829 AN: 1404942 Hom.: 6 Cov.: 32 AF XY: 0.000564 AC XY: 391 AN XY: 693548

African (AFR) AF: 0.0183 AC: 587 AN: 31990

American (AMR) AF: 0.00121 AC: 44 AN: 36256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25240

East Asian (EAS) AF: 0.00 AC: 0 AN: 36360

South Asian (SAS) AF: 0.0000880 AC: 7 AN: 79560

European-Finnish (FIN) AF: 0.00154 AC: 76 AN: 49388

Middle Eastern (MID) AF: 0.000702 AC: 4 AN: 5702

European-Non Finnish (NFE) AF: 0.0000249 AC: 27 AN: 1082204

Other (OTH) AF: 0.00144 AC: 84 AN: 58242

GnomAD4 genome AF: 0.00510 AC: 777 AN: 152388 Hom.: 4 Cov.: 33 AF XY: 0.00471 AC XY: 351 AN XY: 74514

African (AFR) AF: 0.0166 AC: 691 AN: 41604

American (AMR) AF: 0.00274 AC: 42 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00311 AC: 33 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68038

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00255 Hom.: 2

Bravo AF: 0.00593

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.94
DANN	Benign	0.59
PhyloP100		-4.8
Mutation Taster		=97/3	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs146662557; hg19: chr4-6037784; COSMIC: COSV104709990;