8-91295613-G-T

Position:

• chr8-91295613-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052832.4(SLC26A7):​c.387G>T​(p.Gln129His) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC26A7 NM_052832.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.603

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07750884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A7	NM_052832.4	c.387G>T	p.Gln129His	missense_variant	4/19	ENST00000276609.8	NP_439897.1
SLC26A7	NM_134266.2	c.387G>T	p.Gln129His	missense_variant	4/19		NP_599028.1
SLC26A7	NM_001282356.2	c.387G>T	p.Gln129His	missense_variant	5/20		NP_001269285.1
SLC26A7	NM_001282357.2	c.-434G>T		5_prime_UTR_variant	5/19		NP_001269286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A7	ENST00000276609.8	c.387G>T	p.Gln129His	missense_variant	4/19	1	NM_052832.4	ENSP00000276609	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Nov 21, 2023

The c.387G>T (p.Q129H) alteration is located in exon 4 (coding exon 3) of the SLC26A7 gene. This alteration results from a G to T substitution at nucleotide position 387, causing the glutamine (Q) at amino acid position 129 to be replaced by a histidine (H). 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	0.077
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Benign	0.87
DEOGEN2	Benign	0.38	.;T;T;T;.
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.55	T;.;T;.;T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.078	T;T;T;T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.9	.;M;M;M;M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.82	N;N;.;N;N
REVEL	Benign	0.12
Sift	Benign	0.60	T;T;.;T;T
Sift4G	Benign	0.45	T;T;T;T;T
Polyphen		0.0	.;B;B;B;B
Vest4		0.23, 0.23, 0.23
MutPred		0.23		Gain of disorder (P = 0.1398);Gain of disorder (P = 0.1398);Gain of disorder (P = 0.1398);Gain of disorder (P = 0.1398);Gain of disorder (P = 0.1398);
MVP		0.54
MPC		0.10
ClinPred		0.027	T
GERP RS		1.5
Varity_R		0.049
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-92307841;