5-157162671-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_130899.3(GARIN3):c.1594A>T(p.Ser532Cys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GARIN3 NM_130899.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.13

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.302072).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GARIN3	NM_130899.3	c.1594A>T	p.Ser532Cys	missense_variant	2/2	ENST00000302938.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GARIN3	ENST00000302938.4	c.1594A>T	p.Ser532Cys	missense_variant	2/2	1	NM_130899.3	P1
ITK	ENST00000521769.5	c.-296-3417T>A		intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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 12, 2023

The c.1594A>T (p.S532C) alteration is located in exon 2 (coding exon 2) of the FAM71B gene. This alteration results from a A to T substitution at nucleotide position 1594, causing the serine (S) at amino acid position 532 to be replaced by a cysteine (C). 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	0.14
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
Cadd	Benign	22
Dann	Uncertain	0.98
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.038
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.12
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.033	D
Polyphen		1.0	D
Vest4		0.43
MutPred		0.17		Gain of methylation at K533 (P = 0.0168);
MVP		0.23
MPC		0.49
ClinPred		0.95	D
GERP RS		2.7
Varity_R		0.13
gMVP		0.17

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: chr5-156589682;