chr5-157162458-T-C

Position:

• chr5-157162458-T-C

Variant summary

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

The NM_130899.3(GARIN3):​c.1807A>G​(p.Lys603Glu) 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. 12/21 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: GARIN3 NM_130899.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.09

Genes affected

GARIN3 (HGNC:28397): (golgi associated RAB2 interactor family member 3) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ITK (HGNC:6171): (IL2 inducible T cell kinase) This gene encodes an intracellular tyrosine kinase expressed in T-cells. The protein contains both SH2 and SH3 domains which are often found in intracellular kinases. It is thought to play a role in T-cell proliferation and differentiation. [provided by RefSeq, Jul 2008]

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=0.20200646).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GARIN3	NM_130899.3	c.1807A>G	p.Lys603Glu	missense_variant	2/2	ENST00000302938.4	NP_570969.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GARIN3	ENST00000302938.4	c.1807A>G	p.Lys603Glu	missense_variant	2/2	1	NM_130899.3	ENSP00000305596	P1
ITK	ENST00000521769.5	c.-296-3630T>C		intron_variant		4		ENSP00000430327

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Aug 08, 2023

The c.1807A>G (p.K603E) alteration is located in exon 2 (coding exon 2) of the FAM71B gene. This alteration results from a A to G substitution at nucleotide position 1807, causing the lysine (K) at amino acid position 603 to be replaced by a glutamic acid (E). 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	0.16
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.00051	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.071
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	0.89	N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.067
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.92	P
Vest4		0.40
MutPred		0.25		Loss of methylation at K603 (P = 0.0068);
MVP		0.055
MPC		0.45
ClinPred		0.97	D
GERP RS		3.0
Varity_R		0.35
gMVP		0.077

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: chr5-156589469;