chr8-91295701-C-G

Position:

• chr8-91295701-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001282357.2(SLC26A7):​c.-346C>G variant causes a 5 prime UTR premature start codon gain change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC26A7 NM_001282357.2 5_prime_UTR_premature_start_codon_gain
• Scores: Splicing: ADA: 0.8660
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.19

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.869

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A7	NM_052832.4	c.475C>G	p.Gln159Glu	missense_variant, splice_region_variant	4/19	ENST00000276609.8	NP_439897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A7	ENST00000276609.8	c.475C>G	p.Gln159Glu	missense_variant, splice_region_variant	4/19	1	NM_052832.4	ENSP00000276609.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 21, 2024

The c.475C>G (p.Q159E) alteration is located in exon 4 (coding exon 3) of the SLC26A7 gene. This alteration results from a C to G substitution at nucleotide position 475, causing the glutamine (Q) at amino acid position 159 to be replaced by a glutamic acid (E). 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	0.21
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.78	.;D;D;D;.
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.86	D;.;D;.;D
M_CAP	Uncertain	0.21	D
MetaRNN	Pathogenic	0.87	D;D;D;D;D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Uncertain	2.2	.;M;M;M;M
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.5	D;D;.;D;D
REVEL	Pathogenic	0.83
Sift	Uncertain	0.0010	D;D;.;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		0.98, 0.99	.;D;D;D;D
Vest4		0.90, 0.91
MutPred		0.67		Loss of MoRF binding (P = 0.3213);Loss of MoRF binding (P = 0.3213);Loss of MoRF binding (P = 0.3213);Loss of MoRF binding (P = 0.3213);Loss of MoRF binding (P = 0.3213);
MVP		0.87
MPC		0.50
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.72
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.87
dbscSNV1_RF	Benign	0.61
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

Other links and lift over

dbSNP: rs1811998928; hg19: chr8-92307929;