rs140210148

Positions:

• chr6-36012301-C-G
• chr6-36012301-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM5

The NM_052961.4(SLC26A8):​c.260G>C​(p.Arg87Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R87Q) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC26A8 NM_052961.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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]

LOC105375034 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr6-36012301-C-T is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A8	NM_052961.4	c.260G>C	p.Arg87Pro	missense_variant	3/20	ENST00000490799.6	NP_443193.1
LOC105375034	XR_926746.3			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A8	ENST00000490799.6	c.260G>C	p.Arg87Pro	missense_variant	3/20	1	NM_052961.4	ENSP00000417638	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.82	.;T;T;T
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.63	D;D;D;D
MetaSVM	Uncertain	0.31	D
MutationAssessor	Benign	1.8	L;L;L;.
MutationTaster	Benign	0.88	D;D;N
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.6	D;N;D;D
REVEL	Uncertain	0.58
Sift	Benign	0.50	T;T;T;T
Sift4G	Uncertain	0.039	D;D;D;T
Polyphen		1.0	D;D;D;.
Vest4		0.63
MutPred		0.53		Loss of ubiquitination at K89 (P = 0.093);Loss of ubiquitination at K89 (P = 0.093);Loss of ubiquitination at K89 (P = 0.093);.;
MVP		0.76
MPC		0.98
ClinPred		0.96	D
GERP RS		4.8
Varity_R		0.77
gMVP		0.84

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-35980078;