Variant chr8-91249726-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001282357.2(SLC26A7):c.-746A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC26A7
NM_001282357.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0110

Variant links:

Genes affected

SLC26A7 (HGNC:14467): (solute carrier family 26 member 7) This gene is one member of a family of sulfate/anion transporter genes. Family members are well conserved in gene structure and protein length yet have markedly different tissue expression patterns. This gene has abundant and specific expression in the kidney. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Aug 2013]

SLC26A7 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.096375376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A7	NM_052832.4 linkuse as main transcript	c.75A>G	p.Ile25Met	missense_variant	2/19	ENST00000276609.8	NP_439897.1	Q8TE54-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A7	ENST00000276609.8 linkuse as main transcript	c.75A>G	p.Ile25Met	missense_variant	2/19	1	NM_052832.4	ENSP00000276609.3		Q8TE54-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248596

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134458

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 SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1458910

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725748

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 03, 2024

The c.75A>G (p.I25M) alteration is located in exon 2 (coding exon 1) of the SLC26A7 gene. This alteration results from a A to G substitution at nucleotide position 75, causing the isoleucine (I) at amino acid position 25 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.36

CADD

Benign

6.5

DANN

Benign

0.63

DEOGEN2

Benign

0.032

.;T;T;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.64

T;.;T;.;T

M_CAP

Benign

0.042

MetaRNN

Benign

0.096

T;T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.0

.;N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

0.44

N;N;.;N;N

REVEL

Benign

0.23

Sift

Benign

0.15

T;T;.;T;T

Sift4G

Uncertain

0.033

D;D;D;D;D

Polyphen

0.0, 0.0010

.;B;B;B;B

Vest4

0.17, 0.17, 0.17, 0.17

MutPred

0.39

Gain of disorder (P = 0.0725);Gain of disorder (P = 0.0725);Gain of disorder (P = 0.0725);Gain of disorder (P = 0.0725);Gain of disorder (P = 0.0725);

MVP

0.37

MPC

0.18

ClinPred

0.039

GERP RS

-5.9

Varity_R

0.073

gMVP

0.31

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

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

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