Genetic Variant STRA6:c.*306C>A (chr15-74195296-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022369.4(STRA6):c.597+6C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,459,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

STRA6
NM_022369.4 splice_region, intron

Scores

Splicing: ADA: 0.0001711

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.758

Publications

1 publications found

Variant links:

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

STRA6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STRA6	NM_022369.4	MANE Select	c.597+6C>A	splice_region intron	N/A	NP_071764.3
STRA6	NM_001142620.2		c.*306C>A	3_prime_UTR	Exon 6 of 6	NP_001136092.1	Q9BX79-2
STRA6	NM_001199042.2		c.714+6C>A	splice_region intron	N/A	NP_001185971.1	Q9BX79-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STRA6	ENST00000432245.6	TSL:1	c.*306C>A	3_prime_UTR	Exon 6 of 6	ENSP00000407176.2	Q9BX79-2
STRA6	ENST00000395105.9	TSL:1 MANE Select	c.597+6C>A	splice_region intron	N/A	ENSP00000378537.4	Q9BX79-1
STRA6	ENST00000563965.5	TSL:1	c.714+6C>A	splice_region intron	N/A	ENSP00000456609.1	Q9BX79-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

249112

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1459580

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726080

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33440

American (AMR)

AF:

0.00

AC:

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26088

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86028

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52692

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4918

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1111786

Other (OTH)

AF:

0.00

AC:

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.1

(source)

DANN

Benign

0.63

PhyloP100

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00017

dbscSNV1_RF

Benign

0.022

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over