chr6-35955469-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_052961.4(SLC26A8):ā€‹c.1915A>Gā€‹(p.Ile639Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,613,794 control chromosomes in the GnomAD database, including 107,216 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: š‘“ 0.42 ( 15087 hom., cov: 31)
Exomes š‘“: 0.35 ( 92129 hom. )

Consequence

SLC26A8
NM_052961.4 missense

Scores

18

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.34
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=2.815994E-6).
BP6
Variant 6-35955469-T-C is Benign according to our data. Variant chr6-35955469-T-C is described in ClinVar as [Benign]. Clinvar id is 1234924.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC26A8NM_052961.4 linkuse as main transcriptc.1915A>G p.Ile639Val missense_variant 17/20 ENST00000490799.6 NP_443193.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC26A8ENST00000490799.6 linkuse as main transcriptc.1915A>G p.Ile639Val missense_variant 17/201 NM_052961.4 ENSP00000417638 P1Q96RN1-1

Frequencies

GnomAD3 genomes
AF:
0.420
AC:
63777
AN:
151864
Hom.:
15044
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.646
Gnomad AMI
AF:
0.407
Gnomad AMR
AF:
0.323
Gnomad ASJ
AF:
0.318
Gnomad EAS
AF:
0.295
Gnomad SAS
AF:
0.292
Gnomad FIN
AF:
0.308
Gnomad MID
AF:
0.462
Gnomad NFE
AF:
0.345
Gnomad OTH
AF:
0.428
GnomAD3 exomes
AF:
0.335
AC:
84110
AN:
251336
Hom.:
15475
AF XY:
0.333
AC XY:
45172
AN XY:
135832
show subpopulations
Gnomad AFR exome
AF:
0.650
Gnomad AMR exome
AF:
0.215
Gnomad ASJ exome
AF:
0.324
Gnomad EAS exome
AF:
0.296
Gnomad SAS exome
AF:
0.285
Gnomad FIN exome
AF:
0.315
Gnomad NFE exome
AF:
0.350
Gnomad OTH exome
AF:
0.345
GnomAD4 exome
AF:
0.349
AC:
510559
AN:
1461812
Hom.:
92129
Cov.:
43
AF XY:
0.346
AC XY:
251855
AN XY:
727204
show subpopulations
Gnomad4 AFR exome
AF:
0.656
Gnomad4 AMR exome
AF:
0.230
Gnomad4 ASJ exome
AF:
0.325
Gnomad4 EAS exome
AF:
0.280
Gnomad4 SAS exome
AF:
0.283
Gnomad4 FIN exome
AF:
0.318
Gnomad4 NFE exome
AF:
0.354
Gnomad4 OTH exome
AF:
0.356
GnomAD4 genome
AF:
0.420
AC:
63863
AN:
151982
Hom.:
15087
Cov.:
31
AF XY:
0.414
AC XY:
30730
AN XY:
74266
show subpopulations
Gnomad4 AFR
AF:
0.647
Gnomad4 AMR
AF:
0.323
Gnomad4 ASJ
AF:
0.318
Gnomad4 EAS
AF:
0.295
Gnomad4 SAS
AF:
0.291
Gnomad4 FIN
AF:
0.308
Gnomad4 NFE
AF:
0.345
Gnomad4 OTH
AF:
0.429
Alfa
AF:
0.360
Hom.:
26053
Bravo
AF:
0.435
TwinsUK
AF:
0.357
AC:
1324
ALSPAC
AF:
0.361
AC:
1390
ESP6500AA
AF:
0.637
AC:
2807
ESP6500EA
AF:
0.349
AC:
3003
ExAC
AF:
0.346
AC:
41971
Asia WGS
AF:
0.309
AC:
1074
AN:
3478
EpiCase
AF:
0.359
EpiControl
AF:
0.358

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxNov 12, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.063
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
0.0010
DANN
Benign
0.28
DEOGEN2
Benign
0.096
T;.;T
Eigen
Benign
-1.9
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.014
N
LIST_S2
Benign
0.25
.;T;T
MetaRNN
Benign
0.0000028
T;T;T
MetaSVM
Benign
-0.57
T
MutationAssessor
Benign
0.46
N;.;N
MutationTaster
Benign
1.0
P;P;P
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.020
N;N;N
REVEL
Benign
0.21
Sift
Benign
0.98
T;T;T
Sift4G
Benign
0.41
T;T;T
Polyphen
0.0
B;B;B
Vest4
0.028
MPC
0.18
ClinPred
0.00059
T
GERP RS
-5.0
Varity_R
0.023
gMVP
0.37

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2295852; hg19: chr6-35923246; COSMIC: COSV62884916; COSMIC: COSV62884916; API