NM_022369.4:c.367G>T

Variant names:

• chr15-74196047-C-A
• rs115067613
• NM_022369.4:c.367G>T

Variant summary

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

The NM_022369.4(STRA6):​c.367G>T​(p.Ala123Ser) 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. 17/22 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. A123P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STRA6 NM_022369.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08
• Publications: 1 publications found

Genes affected

STRA6 (HGNC:30650): (signaling receptor and transporter of retinol STRA6) The protein encoded by this gene is a membrane protein involved in the metabolism of retinol. The encoded protein acts as a receptor for retinol/retinol binding protein complexes. This protein removes the retinol from the complex and transports it across the cell membrane. Defects in this gene are a cause of syndromic microphthalmia type 9 (MCOPS9). Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

STRA6 Gene-Disease associations (from GenCC):

• Matthew-Wood syndrome

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Orphanet
• microphthalmia, isolated, with coloboma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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=0.1300458).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022369.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRA6	NM_022369.4	MANE Select	c.367G>T	p.Ala123Ser	missense	Exon 5 of 19	NP_071764.3
	STRA6	NM_001199042.2		c.484G>T	p.Ala162Ser	missense	Exon 5 of 19	NP_001185971.1
	STRA6	NM_001199040.2		c.478G>T	p.Ala160Ser	missense	Exon 5 of 19	NP_001185969.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRA6	ENST00000395105.9	TSL:1 MANE Select	c.367G>T	p.Ala123Ser	missense	Exon 5 of 19	ENSP00000378537.4
	STRA6	ENST00000563965.5	TSL:1	c.484G>T	p.Ala162Ser	missense	Exon 5 of 19	ENSP00000456609.1
	STRA6	ENST00000423167.6	TSL:1	c.340G>T	p.Ala114Ser	missense	Exon 5 of 19	ENSP00000413012.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.077	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.1
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.25	N
REVEL	Benign	0.18
Sift	Uncertain	0.015	D
Sift4G	Benign	0.29	T
Polyphen		0.059	B
Vest4		0.11
MutPred		0.38		Gain of glycosylation at A123 (P = 0.0411)
MVP		0.73
MPC		0.091
ClinPred		0.52	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.067
gMVP		0.51
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs115067613; hg19: chr15-74488388;