6-35955178-A-G

Position:

• chr6-35955178-A-G

Variant summary

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

The NM_052961.4(SLC26A8):​c.2206T>C​(p.Ser736Pro) 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. 14/21 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: SLC26A8 NM_052961.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.84

Genes affected

SLC26A8 (HGNC:14468): (solute carrier family 26 member 8) This gene encodes a member of the SLC26 gene family of anion transporters. Family members are well conserved in gene structure and protein length yet have markedly different tissue expression patterns. The expression of this gene appears to be restricted to spermatocytes. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Jul 2010]

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=0.2071192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A8	NM_052961.4	c.2206T>C	p.Ser736Pro	missense_variant	17/20	ENST00000490799.6	NP_443193.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A8	ENST00000490799.6	c.2206T>C	p.Ser736Pro	missense_variant	17/20	1	NM_052961.4	ENSP00000417638	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 16, 2024

The c.2206T>C (p.S736P) alteration is located in exon 17 (coding exon 16) of the SLC26A8 gene. This alteration results from a T to C substitution at nucleotide position 2206, causing the serine (S) at amino acid position 736 to be replaced by a proline (P). 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	0.085
BayesDel_addAF	Uncertain	0.084	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	0.016
DANN	Benign	0.76
DEOGEN2	Benign	0.30	T;.;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.38	.;T;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	0.69	N;.;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Uncertain	0.51
Sift	Benign	0.074	T;T;T
Sift4G	Benign	0.28	T;T;T
Polyphen		0.0020	B;B;B
Vest4		0.16
MutPred		0.76		Gain of helix (P = 0.132);.;Gain of helix (P = 0.132);
MVP		0.28
MPC		0.27
ClinPred		0.12	T
GERP RS		-9.2
Varity_R		0.19
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1772008967; hg19: chr6-35922955;