Variant 2-85344310-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_017750.4(RETSAT):c.1295C>T(p.Ala432Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,614,048 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. A432A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0043 ( 13 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 118 hom. )

Consequence

RETSAT
NM_017750.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.26

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017447174).

BP6

Variant 2-85344310-G-A is Benign according to our data. Variant chr2-85344310-G-A is described in ClinVar as [Benign]. Clinvar id is 771335.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RETSAT	NM_017750.4 linkuse as main transcript	c.1295C>T	p.Ala432Val	missense_variant	8/11	ENST00000295802.9
RETSAT	XM_047444828.1 linkuse as main transcript	c.1295C>T	p.Ala432Val	missense_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RETSAT	ENST00000295802.9 linkuse as main transcript	c.1295C>T	p.Ala432Val	missense_variant	8/11	1	NM_017750.4	P1	Q6NUM9-1
RETSAT	ENST00000429806.5 linkuse as main transcript	c.812C>T	p.Ala271Val	missense_variant, NMD_transcript_variant	6/8	1
RETSAT	ENST00000449375.1 linkuse as main transcript	c.662C>T	p.Ala221Val	missense_variant	5/8	5
RETSAT	ENST00000438611.4 linkuse as main transcript	c.*437C>T		3_prime_UTR_variant, NMD_transcript_variant	4/6	5

Frequencies

GnomAD3 genomes

AF:

0.00426

AC:

648

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0170

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.0610

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00480

GnomAD3 exomes

AF:

0.0109

AC:

2750

AN:

251446

Hom.:

AF XY:

0.00909

AC XY:

1235

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.0391

Gnomad ASJ exome

AF:

0.000992

Gnomad EAS exome

AF:

0.0678

Gnomad SAS exome

AF:

0.000947

Gnomad FIN exome

AF:

0.00245

Gnomad NFE exome

AF:

0.000193

Gnomad OTH exome

AF:

0.00521

GnomAD4 exome

AF:

0.00322

AC:

4713

AN:

1461830

Hom.:

118

Cov.:

AF XY:

0.00300

AC XY:

2185

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.0366

Gnomad4 ASJ exome

AF:

0.00130

Gnomad4 EAS exome

AF:

0.0637

Gnomad4 SAS exome

AF:

0.00128

Gnomad4 FIN exome

AF:

0.00137

Gnomad4 NFE exome

AF:

0.000106

Gnomad4 OTH exome

AF:

0.00339

GnomAD4 genome

AF:

0.00427

AC:

650

AN:

152218

Hom.:

Cov.:

AF XY:

0.00480

AC XY:

357

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.0169

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.0615

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00207

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00475

Alfa

AF:

0.000942

Hom.:

Bravo

AF:

0.00709

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00906

AC:

1100

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0073

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.60

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.95

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.8

REVEL

Benign

0.033

Sift

Benign

0.19

Sift4G

Benign

0.17

Polyphen

0.015

Vest4

0.15

MPC

0.072

ClinPred

0.0064

GERP RS

-0.63

Varity_R

0.065

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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