rs201709908

Variant summary

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

The NM_000441.2(SLC26A4):​c.1796C>A​(p.Ala599Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000695 in 1,439,478 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A599V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC26A4
NM_000441.2 missense

Scores

1
11
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.43
Variant links:
Genes affected
SLC26A4 (HGNC:8818): (solute carrier family 26 member 4) Mutations in this gene are associated with Pendred syndrome, the most common form of syndromic deafness, an autosomal-recessive disease. It is highly homologous to the SLC26A3 gene; they have similar genomic structures and this gene is located 3' of the SLC26A3 gene. The encoded protein has homology to sulfate transporters. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons MANE UniProt
SLC26A4NM_000441.2 linkuse as main transcriptc.1796C>A p.Ala599Glu missense_variant 16/21 ENST00000644269.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC26A4ENST00000644269.2 linkuse as main transcriptc.1796C>A p.Ala599Glu missense_variant 16/21 NM_000441.2 P1O43511-1
SLC26A4ENST00000480841.5 linkuse as main transcriptn.645C>A non_coding_transcript_exon_variant 7/83
SLC26A4ENST00000644846.1 linkuse as main transcriptc.509C>A p.Ala170Glu missense_variant, NMD_transcript_variant 6/10
SLC26A4ENST00000492030.2 linkuse as main transcriptn.91-638C>A intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251090
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135690
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.95e-7
AC:
1
AN:
1439478
Hom.:
0
Cov.:
26
AF XY:
0.00000139
AC XY:
1
AN XY:
717698
show subpopulations
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:
9.16e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00000577
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.44
BayesDel_addAF
Pathogenic
0.16
D
BayesDel_noAF
Uncertain
0.0
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.35
T;T
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.82
.;T
M_CAP
Uncertain
0.12
D
MetaRNN
Uncertain
0.49
T;T
MetaSVM
Uncertain
0.60
D
MutationAssessor
Benign
1.1
L;L
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-2.2
N;.
REVEL
Uncertain
0.61
Sift
Benign
0.47
T;.
Sift4G
Benign
0.50
T;.
Polyphen
0.74
P;P
Vest4
0.61
MutPred
0.44
Gain of solvent accessibility (P = 0.0246);Gain of solvent accessibility (P = 0.0246);
MVP
0.98
MPC
0.059
ClinPred
0.79
D
GERP RS
5.7
Varity_R
0.39
gMVP
0.68

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: rs201709908; hg19: chr7-107341634; API