Variant chr19-50475859-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001308429.2(GARIN5A):c.334C>G(p.Pro112Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

GARIN5A
NM_001308429.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.673

Variant links:

Genes affected

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

GARIN5A links:

GARIN5A (HGNC:):

GARIN5A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.2638929).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GARIN5A	NM_001308429.2 linkuse as main transcript	c.334C>G	p.Pro112Ala	missense_variant	2/5	ENST00000600100.6	NP_001295358.1	Q6IPT2-1
GARIN5A	NM_138411.3 linkuse as main transcript	c.334C>G	p.Pro112Ala	missense_variant	2/5		NP_612420.1	Q6IPT2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GARIN5A	ENST00000600100.6 linkuse as main transcript	c.334C>G	p.Pro112Ala	missense_variant	2/5	1	NM_001308429.2	ENSP00000472421.2		Q6IPT2-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250852

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135686

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461646

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2022

The c.334C>G (p.P112A) alteration is located in exon 2 (coding exon 2) of the FAM71E1 gene. This alteration results from a C to G substitution at nucleotide position 334, causing the proline (P) at amino acid position 112 to be replaced by an alanine (A). 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

0.17

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.19

T;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.26

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L

PrimateAI

Benign

0.39

Sift4G

Uncertain

0.021

D;T

Polyphen

0.91

P;P

Vest4

0.36

MutPred

0.79

Loss of stability (P = 0.0475);Loss of stability (P = 0.0475);

MVP

0.10

MPC

0.19

ClinPred

0.075

GERP RS

-0.39

Varity_R

0.11

gMVP

0.66

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over