dbSNP rs140210148: SLC26A8:p.Arg87Pro (chr6-36012301-C-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PM5

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 Pathogenic.

Frequency

Genomes: not found (cov: 32)

Consequence

SLC26A8
NM_052961.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.15

Publications

0 publications found

Variant links:

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]

SLC26A8 Gene-Disease associations (from GenCC):

non-syndromic male infertility due to sperm motility disorder
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
spermatogenic failure 3
Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

SLC26A8 links:

LOC105375034 (HGNC:):

LOC105375034 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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 ClinVar as Pathogenic. ClinVar VariationId is 50909.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052961.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC26A8	NM_052961.4	MANE Select	c.260G>C	p.Arg87Pro	missense	Exon 3 of 20	NP_443193.1
SLC26A8	NM_001193476.2		c.260G>C	p.Arg87Pro	missense	Exon 3 of 20	NP_001180405.1
SLC26A8	NM_138718.3		c.260G>C	p.Arg87Pro	missense	Exon 3 of 18	NP_619732.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC26A8	ENST00000490799.6	TSL:1 MANE Select	c.260G>C	p.Arg87Pro	missense	Exon 3 of 20	ENSP00000417638.1
SLC26A8	ENST00000394602.6	TSL:1	c.260G>C	p.Arg87Pro	missense	Exon 3 of 18	ENSP00000378100.2
SLC26A8	ENST00000355574.6	TSL:2	c.260G>C	p.Arg87Pro	missense	Exon 3 of 20	ENSP00000347778.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.82

M_CAP

Uncertain

0.24

MetaRNN

Uncertain

0.63

MetaSVM

Uncertain

0.31

MutationAssessor

Benign

1.8

PhyloP100

1.1

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.58

Sift

Benign

0.50

Sift4G

Uncertain

0.039

Polyphen

1.0

Vest4

0.63

MutPred

0.53

Loss of ubiquitination at K89 (P = 0.093)

MVP

0.76

MPC

0.98

ClinPred

0.96

GERP RS

4.8

Varity_R

0.77

gMVP

0.84

Mutation Taster

=53/47

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over