rs13384912

Variant names:

• chr2-85343657-G-T
• rs13384912
• NM_017750.4:c.1675C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-85343657-G-T
• chr2-85343657-G-A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_017750.4(RETSAT):​c.1675C>A​(p.Pro559Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000291 in 1,461,126 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (5 hom., cov: 35)
  • Exomes 𝑓: 0.00029 (6 hom.)
  • Failed GnomAD Quality Control
• Consequence: RETSAT NM_017750.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.67
• Publications: 2 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.021759927).
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

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.1675C>A	p.Pro559Thr	missense	Exon 10 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.1675C>A	p.Pro559Thr	missense	Exon 10 of 11	ENSP00000295802.4	Q6NUM9-1
	RETSAT	ENST00000429806.5	TSL:1	n.*62C>A		non_coding_transcript_exon	Exon 7 of 8	ENSP00000388202.1	H7BZ81
	RETSAT	ENST00000429806.5	TSL:1	n.*62C>A		3_prime_UTR	Exon 7 of 8	ENSP00000388202.1	H7BZ81

Frequencies

GnomAD3 genomes AF: 0.00383 AC: 573 AN: 149448 Hom.: 5 Cov.: 35

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00114

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000795

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000297

Gnomad OTH AF: 0.00489

GnomAD2 exomes AF: 0.000112 AC: 28 AN: 250800 AF XY: 0.000103

Gnomad AFR exome AF: 0.000249

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000979

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000291 AC: 425 AN: 1461126 Hom.: 6 Cov.: 31 AF XY: 0.000261 AC XY: 190 AN XY: 726874

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00791 AC: 263 AN: 33258

American (AMR) AF: 0.000537 AC: 24 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.000529 AC: 21 AN: 39666

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5764

European-Non Finnish (NFE) AF: 0.0000540 AC: 60 AN: 1111682

Other (OTH) AF: 0.000729 AC: 44 AN: 60330

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00384 AC: 574 AN: 149570 Hom.: 5 Cov.: 35 AF XY: 0.00346 AC XY: 253 AN XY: 73146

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0129 AC: 522 AN: 40320

American (AMR) AF: 0.00114 AC: 17 AN: 14974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3438

East Asian (EAS) AF: 0.000797 AC: 4 AN: 5020

South Asian (SAS) AF: 0.00 AC: 0 AN: 4716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10468

Middle Eastern (MID) AF: 0.00355 AC: 1 AN: 282

European-Non Finnish (NFE) AF: 0.000297 AC: 20 AN: 67380

Other (OTH) AF: 0.00484 AC: 10 AN: 2068

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000184 Hom.: 0

ExAC AF: 0.0000659 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.7
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.18
Sift	Benign	0.037	D
Sift4G	Uncertain	0.011	D
Polyphen		0.76	P
Vest4		0.31
MVP		0.48
MPC		0.15
ClinPred		0.14	T
GERP RS		4.1
Varity_R		0.22
gMVP		0.56
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs13384912; hg19: chr2-85570780; COSMIC: COSV55529147; COSMIC: COSV55529147;