chr2-85344042-G-A

Position:

• chr2-85344042-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017750.4(RETSAT):​c.1490C>T​(p.Ser497Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RETSAT NM_017750.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.06

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]

ACMG classification

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=0.22721037).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RETSAT	NM_017750.4	c.1490C>T	p.Ser497Phe	missense_variant	9/11	ENST00000295802.9
RETSAT	XM_047444828.1	c.1366+197C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RETSAT	ENST00000295802.9	c.1490C>T	p.Ser497Phe	missense_variant	9/11	1	NM_017750.4	P1
RETSAT	ENST00000429806.5	c.881+197C>T		intron_variant, NMD_transcript_variant		1
RETSAT	ENST00000449375.1	c.857C>T	p.Ser286Phe	missense_variant	6/8	5
RETSAT	ENST00000438611.4	c.*508+197C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2023

The c.1490C>T (p.S497F) alteration is located in exon 9 (coding exon 9) of the RETSAT gene. This alteration results from a C to T substitution at nucleotide position 1490, causing the serine (S) at amino acid position 497 to be replaced by a phenylalanine (F). 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	Uncertain	0.43
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.0010	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.11
Sift	Benign	0.18	T
Sift4G	Benign	0.10	T
Polyphen		0.0080	B
Vest4		0.48
MutPred		0.61		Loss of disorder (P = 0.052);
MVP		0.085
MPC		0.091
ClinPred		0.074	T
GERP RS		-0.54
Varity_R		0.044
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-85571165;