19-50476142-C-T

Position:

• chr19-50476142-C-T

Variant summary

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

The NM_001308429.2(GARIN5A):​c.247G>A​(p.Gly83Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GARIN5A NM_001308429.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0130

Genes affected

GARIN5A (HGNC:25107): (golgi associated RAB2 interactor 5A)

GARIN5A (HGNC:):

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=0.08188626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GARIN5A	NM_001308429.2	c.247G>A	p.Gly83Ser	missense_variant	1/5	ENST00000600100.6	NP_001295358.1
GARIN5A	NM_138411.3	c.247G>A	p.Gly83Ser	missense_variant	1/5		NP_612420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GARIN5A	ENST00000600100.6	c.247G>A	p.Gly83Ser	missense_variant	1/5	1	NM_001308429.2	ENSP00000472421.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461230 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726908

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Jul 02, 2024

The c.247G>A (p.G83S) alteration is located in exon 1 (coding exon 1) of the FAM71E1 gene. This alteration results from a G to A substitution at nucleotide position 247, causing the glycine (G) at amino acid position 83 to be replaced by a serine (S). 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	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	T;.
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.082	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L;L
PrimateAI	Benign	0.39	T
Sift4G	Benign	0.40	T;T
Polyphen		0.82	P;P
Vest4		0.10
MutPred		0.12		Gain of glycosylation at G83 (P = 7e-04);Gain of glycosylation at G83 (P = 7e-04);
MVP		0.030
MPC		0.34
ClinPred		0.60	D
GERP RS		3.3
Varity_R		0.12
gMVP		0.13

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: chr19-50979399;