rs114153657

Variant names:

• chr6-35951210-C-G
• rs114153657
• NM_052961.4:c.2425G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-35951210-C-G
• chr6-35951210-C-T

Variant summary

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

The NM_052961.4(SLC26A8):​c.2425G>C​(p.Asp809His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,612,516 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC26A8 NM_052961.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.61

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A8	NM_052961.4	c.2425G>C	p.Asp809His	missense_variant	Exon 19 of 20	ENST00000490799.6	NP_443193.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A8	ENST00000490799.6	c.2425G>C	p.Asp809His	missense_variant	Exon 19 of 20	1	NM_052961.4	ENSP00000417638.1

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151454 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461062 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 726816

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151454 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 73912

Gnomad4 AFR AF: 0.0000243

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T;.;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.79	.;T;T
M_CAP	Uncertain	0.26	D
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Uncertain	0.71	D
MutationAssessor	Uncertain	2.2	M;.;M
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.2	D;D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.53
MutPred		0.21		Loss of phosphorylation at S804 (P = 0.132);.;Loss of phosphorylation at S804 (P = 0.132);
MVP		0.81
MPC		0.88
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.34
gMVP		0.57

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

Other links and lift over

dbSNP: rs114153657; hg19: chr6-35918987;