4-6080297-C-T

Position:

• chr4-6080297-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001099433.2(JAKMIP1):​c.1117G>A​(p.Ala373Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: JAKMIP1 NM_001099433.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.419

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048796505).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JAKMIP1	NM_001099433.2	c.1117G>A	p.Ala373Thr	missense_variant	7/21	ENST00000409021.9
JAKMIP1	NM_001306133.2	c.1117G>A	p.Ala373Thr	missense_variant	7/13
JAKMIP1	NM_144720.4	c.1117G>A	p.Ala373Thr	missense_variant	7/13
JAKMIP1	NM_001306134.2	c.622G>A	p.Ala208Thr	missense_variant	6/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAKMIP1	ENST00000409021.9	c.1117G>A	p.Ala373Thr	missense_variant	7/21	1	NM_001099433.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 02, 2021

The c.1117G>A (p.A373T) alteration is located in exon 7 (coding exon 6) of the JAKMIP1 gene. This alteration results from a G to A substitution at nucleotide position 1117, causing the alanine (A) at amino acid position 373 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	.;.;T;T;.
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.85	D;D;.;T;D
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.049	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N;.;N;N;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.37	N;N;N;N;N
REVEL	Benign	0.030
Sift	Benign	0.38	T;T;T;T;T
Sift4G	Benign	0.086	T;T;T;T;T
Polyphen		0.0030	B;B;B;B;.
Vest4		0.12
MutPred		0.10		Gain of glycosylation at A373 (P = 0.0424);.;Gain of glycosylation at A373 (P = 0.0424);Gain of glycosylation at A373 (P = 0.0424);.;
MVP		0.29
MPC		0.64
ClinPred		0.11	T
GERP RS		3.6
Varity_R		0.034
gMVP		0.11

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

LitVar

Other links and lift over

dbSNP: rs199727362; hg19: chr4-6082024;