Variant 2-85343657-G-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.1675C>A(p.Pro559Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000291 in 1,461,126 control chromosomes in the GnomAD database, including 6 homozygotes. 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 (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0038 ( 5 hom., cov: 35)

Exomes 𝑓: 0.00029 ( 6 hom. )

Failed GnomAD Quality Control

Consequence

RETSAT
NM_017750.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.67

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=0.021759927).

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RETSAT	NM_017750.4 linkuse as main transcript	c.1675C>A	p.Pro559Thr	missense_variant	10/11	ENST00000295802.9
RETSAT	XM_047444828.1 linkuse as main transcript	c.*62C>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.1675C>A	p.Pro559Thr	missense_variant	10/11	1	NM_017750.4	P1	Q6NUM9-1
RETSAT	ENST00000429806.5 linkuse as main transcript	c.*62C>A		3_prime_UTR_variant, NMD_transcript_variant	7/8	1
RETSAT	ENST00000449375.1 linkuse as main transcript	c.1042C>A	p.Pro348Thr	missense_variant	7/8	5
RETSAT	ENST00000438611.4 linkuse as main transcript	c.*650C>A		3_prime_UTR_variant, NMD_transcript_variant	5/6	5

Frequencies

GnomAD3 genomes

AF:

0.00383

AC:

573

AN:

149448

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00114

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000795

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000297

Gnomad OTH

AF:

0.00489

GnomAD3 exomes

AF:

0.000112

AC:

AN:

250800

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135628

show subpopulations

Gnomad AFR exome

AF:

0.000249

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000979

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000291

AC:

425

AN:

1461126

Hom.:

Cov.:

AF XY:

0.000261

AC XY:

190

AN XY:

726874

show subpopulations

Gnomad4 AFR exome

AF:

0.00791

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000529

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000540

Gnomad4 OTH exome

AF:

0.000729

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00384

AC:

574

AN:

149570

Hom.:

Cov.:

AF XY:

0.00346

AC XY:

253

AN XY:

73146

show subpopulations

Gnomad4 AFR

AF:

0.0129

Gnomad4 AMR

AF:

0.00114

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000797

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000297

Gnomad4 OTH

AF:

0.00484

Alfa

AF:

0.000184

Hom.:

ExAC

AF:

0.0000659

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.1675C>A (p.P559T) alteration is located in exon 10 (coding exon 10) of the RETSAT gene. This alteration results from a C to A substitution at nucleotide position 1675, causing the proline (P) at amino acid position 559 to be replaced by a threonine (T). 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

0.10

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

0.13

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.65

M_CAP

Benign

0.073

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-4.9

REVEL

Benign

0.18

Sift

Benign

0.037

Sift4G

Uncertain

0.011

Polyphen

0.76

Vest4

0.31

MVP

0.48

MPC

0.15

ClinPred

0.14

GERP RS

4.1

Varity_R

0.22

gMVP

0.56

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