Variant chr2-85343375-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_017750.4(RETSAT):c.1700A>G(p.Asp567Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000893 in 1,612,296 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D567Y) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 36)

Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

RETSAT
NM_017750.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.40

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RETSAT	NM_017750.4 linkuse as main transcript	c.1700A>G	p.Asp567Gly	missense_variant	11/11	ENST00000295802.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RETSAT	ENST00000295802.9 linkuse as main transcript	c.1700A>G	p.Asp567Gly	missense_variant	11/11	1	NM_017750.4	P1	Q6NUM9-1
RETSAT	ENST00000429806.5 linkuse as main transcript	c.*87A>G		3_prime_UTR_variant, NMD_transcript_variant	8/8	1
RETSAT	ENST00000449375.1 linkuse as main transcript	c.1067A>G	p.Asp356Gly	missense_variant	8/8	5
RETSAT	ENST00000438611.4 linkuse as main transcript	c.*675A>G		3_prime_UTR_variant, NMD_transcript_variant	6/6	5

Frequencies

GnomAD3 genomes

AF:

0.0000985

AC:

AN:

152294

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.0110

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000320

AC:

AN:

250104

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135326

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000620

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000884

AC:

129

AN:

1460002

Hom.:

Cov.:

AF XY:

0.0000868

AC XY:

AN XY:

726122

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.000114

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74406

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Apr 25, 2023

The c.1700A>G (p.D567G) alteration is located in exon 11 (coding exon 11) of the RETSAT gene. This alteration results from a A to G substitution at nucleotide position 1700, causing the aspartic acid (D) at amino acid position 567 to be replaced by a glycine (G). 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

Pathogenic

0.86

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.76

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.43

MetaSVM

Uncertain

-0.16

MutationAssessor

Pathogenic

3.4

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-6.2

REVEL

Uncertain

0.54

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.90

MutPred

0.65

Gain of catalytic residue at G565 (P = 0.0317);

MVP

0.50

MPC

0.46

ClinPred

0.96

GERP RS

3.9

Varity_R

0.77

gMVP

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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