Variant chr21-42496229-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000419522.5(SLC37A1):c.-301G>A variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,609,598 control chromosomes in the GnomAD database, including 124,837 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 9514 hom., cov: 33)

Exomes 𝑓: 0.39 ( 115323 hom. )

Consequence

SLC37A1
ENST00000419522.5 splice_region

Scores

Splicing: ADA: 0.00007446

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.487

Variant links:

Genes affected

SLC37A1 (HGNC:11024): (solute carrier family 37 member 1) The protein encoded by this gene localizes to the endoplasmic reticulum (ER) membrane. This protein translocates glucose-6-phosphate from the cytoplasm into the lumen of the ER for hydrolysis into glucose by another ER membrane protein. This gene is a member of the solute carrier 37 gene family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

SLC37A1 links:

SLC37A1 (HGNC:):

SLC37A1 links:

RSPH1 (HGNC:12371): (radial spoke head component 1) This gene encodes a male meiotic metaphase chromosome-associated acidic protein. This gene is expressed in tissues with motile cilia or flagella, including the trachea, lungs, airway brushings, and testes. Mutations in this gene result in primary ciliary dyskinesia-24. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

RSPH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 21-42496229-G-A is Benign according to our data. Variant chr21-42496229-G-A is described in ClinVar as [Benign]. Clinvar id is 1297838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH1	NM_080860.4 linkuse as main transcript	c.-43C>T		upstream_gene_variant		ENST00000291536.8	NP_543136.1	Q8WYR4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPH1	ENST00000291536.8 linkuse as main transcript	c.-43C>T		upstream_gene_variant		1	NM_080860.4	ENSP00000291536.3		Q8WYR4-1

Frequencies

GnomAD3 genomes

AF:

0.325

AC:

49358

AN:

152064

Hom.:

9512

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.478

Gnomad AMR

AF:

0.536

Gnomad ASJ

AF:

0.358

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.382

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.395

Gnomad OTH

AF:

0.345

GnomAD3 exomes

AF:

0.383

AC:

94820

AN:

247690

Hom.:

20830

AF XY:

0.374

AC XY:

50249

AN XY:

134398

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.674

Gnomad ASJ exome

AF:

0.344

Gnomad EAS exome

AF:

0.197

Gnomad SAS exome

AF:

0.292

Gnomad FIN exome

AF:

0.388

Gnomad NFE exome

AF:

0.388

Gnomad OTH exome

AF:

0.387

GnomAD4 exome

AF:

0.389

AC:

566569

AN:

1457416

Hom.:

115323

Cov.:

AF XY:

0.384

AC XY:

278812

AN XY:

725140

show subpopulations

Gnomad4 AFR exome

AF:

0.116

Gnomad4 AMR exome

AF:

0.653

Gnomad4 ASJ exome

AF:

0.345

Gnomad4 EAS exome

AF:

0.184

Gnomad4 SAS exome

AF:

0.296

Gnomad4 FIN exome

AF:

0.385

Gnomad4 NFE exome

AF:

0.404

Gnomad4 OTH exome

AF:

0.369

GnomAD4 genome

AF:

0.324

AC:

49378

AN:

152182

Hom.:

9514

Cov.:

AF XY:

0.327

AC XY:

24302

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.129

Gnomad4 AMR

AF:

0.536

Gnomad4 ASJ

AF:

0.358

Gnomad4 EAS

AF:

0.194

Gnomad4 SAS

AF:

0.298

Gnomad4 FIN

AF:

0.382

Gnomad4 NFE

AF:

0.395

Gnomad4 OTH

AF:

0.341

Alfa

AF:

0.395

Hom.:

5689

Bravo

AF:

0.330

Asia WGS

AF:

0.244

AC:

853

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Primary ciliary dyskinesia 24

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.3

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000074

dbscSNV1_RF

Benign

0.0080

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over