NM_017750.4:c.1813G>C

Variant names:

• chr2-85343262-C-G
• rs753331463
• NM_017750.4:c.1813G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017750.4(RETSAT):​c.1813G>C​(p.Ala605Pro) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A605T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 36)
• Consequence: RETSAT NM_017750.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14223465).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017750.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RETSAT	NM_017750.4	MANE Select	c.1813G>C	p.Ala605Pro	missense	Exon 11 of 11	NP_060220.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RETSAT	ENST00000295802.9	TSL:1 MANE Select	c.1813G>C	p.Ala605Pro	missense	Exon 11 of 11	ENSP00000295802.4	Q6NUM9-1
	RETSAT	ENST00000429806.5	TSL:1	n.*200G>C		non_coding_transcript_exon	Exon 8 of 8	ENSP00000388202.1	H7BZ81
	RETSAT	ENST00000429806.5	TSL:1	n.*200G>C		3_prime_UTR	Exon 8 of 8	ENSP00000388202.1	H7BZ81

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 36

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.0
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.020
Sift	Benign	0.30	T
Sift4G	Benign	0.28	T
Polyphen		0.83	P
Vest4		0.22
MutPred		0.33		Gain of catalytic residue at A605 (P = 0.0347)
MVP		0.18
MPC		0.093
ClinPred		0.34	T
GERP RS		3.0
Varity_R		0.31
gMVP		0.65
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs753331463; hg19: chr2-85570385;