2-85343258-T-G

Position:

• chr2-85343258-T-G

Variant summary

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

The NM_017750.4(RETSAT):​c.1817A>C​(p.Gln606Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 36)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RETSAT NM_017750.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.666

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=0.16459227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RETSAT	NM_017750.4	c.1817A>C	p.Gln606Pro	missense_variant	11/11	ENST00000295802.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RETSAT	ENST00000295802.9	c.1817A>C	p.Gln606Pro	missense_variant	11/11	1	NM_017750.4	P1
RETSAT	ENST00000429806.5	c.*204A>C		3_prime_UTR_variant, NMD_transcript_variant	8/8	1
RETSAT	ENST00000449375.1	c.1184A>C	p.Gln395Pro	missense_variant	8/8	5
RETSAT	ENST00000438611.4	c.*792A>C		3_prime_UTR_variant, NMD_transcript_variant	6/6	5

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461808 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727198

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 36

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

Oct 26, 2022

The c.1817A>C (p.Q606P) alteration is located in exon 11 (coding exon 11) of the RETSAT gene. This alteration results from a A to C substitution at nucleotide position 1817, causing the glutamine (Q) at amino acid position 606 to be replaced by a proline (P). 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	0.092
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	0.91	D;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.055
Sift	Benign	0.070	T
Sift4G	Benign	0.11	T
Polyphen		0.73	P
Vest4		0.29
MutPred		0.24		Gain of glycosylation at Q606 (P = 0.0056);
MVP		0.20
MPC		0.13
ClinPred		0.14	T
GERP RS		1.7
Varity_R		0.19
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr2-85570381;