Variant 2-85343674-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017750.4(RETSAT):c.1658G>A(p.Arg553Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000682 in 1,607,632 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0045 ( 7 hom., cov: 35)

Exomes 𝑓: 0.00030 ( 6 hom. )

Consequence

RETSAT
NM_017750.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.78

Variant links:

Genes affected

RETSAT (HGNC:25991): (retinol saturase) Predicted to enable all-trans-retinol 13,14-reductase activity. Predicted to be involved in retinol metabolic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

RETSAT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.027621746).

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RETSAT	NM_017750.4 linkuse as main transcript	c.1658G>A	p.Arg553Lys	missense_variant	10/11	ENST00000295802.9
RETSAT	XM_047444828.1 linkuse as main transcript	c.*45G>A		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RETSAT	ENST00000295802.9 linkuse as main transcript	c.1658G>A	p.Arg553Lys	missense_variant	10/11	1	NM_017750.4	P1	Q6NUM9-1
RETSAT	ENST00000429806.5 linkuse as main transcript	c.*45G>A		3_prime_UTR_variant, NMD_transcript_variant	7/8	1
RETSAT	ENST00000449375.1 linkuse as main transcript	c.1025G>A	p.Arg342Lys	missense_variant	7/8	5
RETSAT	ENST00000438611.4 linkuse as main transcript	c.*633G>A		3_prime_UTR_variant, NMD_transcript_variant	5/6	5

Frequencies

GnomAD3 genomes

AF:

0.00448

AC:

662

AN:

147932

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0153

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00122

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:

0.000314

Gnomad OTH

AF:

0.00549

GnomAD3 exomes

AF:

0.0000558

AC:

AN:

250676

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

135576

show subpopulations

Gnomad AFR exome

AF:

0.000626

Gnomad AMR exome

AF:

0.00

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:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000297

AC:

433

AN:

1459580

Hom.:

Cov.:

AF XY:

0.000264

AC XY:

192

AN XY:

726152

show subpopulations

Gnomad4 AFR exome

AF:

0.00856

Gnomad4 AMR exome

AF:

0.000673

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:

0.0000657

Gnomad4 OTH exome

AF:

0.000731

GnomAD4 genome

AF:

0.00448

AC:

663

AN:

148052

Hom.:

Cov.:

AF XY:

0.00402

AC XY:

291

AN XY:

72362

show subpopulations

Gnomad4 AFR

AF:

0.0153

Gnomad4 AMR

AF:

0.00122

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000314

Gnomad4 OTH

AF:

0.00543

Alfa

AF:

0.00236

Hom.:

ExAC

AF:

0.000206

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 03, 2022

The c.1658G>A (p.R553K) alteration is located in exon 10 (coding exon 10) of the RETSAT gene. This alteration results from a G to A substitution at nucleotide position 1658, causing the arginine (R) at amino acid position 553 to be replaced by a lysine (K). 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

0.28

BayesDel_addAF

Uncertain

0.029

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.73

M_CAP

Benign

0.031

MetaRNN

Benign

0.028

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.17

Sift

Uncertain

0.011

Sift4G

Uncertain

0.016

Polyphen

0.85

Vest4

0.59

MVP

0.58

MPC

0.39

ClinPred

0.27

GERP RS

5.0

Varity_R

0.55

gMVP

0.82

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