7-107710095-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_000441.2(SLC26A4):​c.2131G>T​(p.Asp711Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000366 in 1,611,582 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

SLC26A4
NM_000441.2 missense

Scores

7
8
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.62
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 4 ACMG points.

PM1
In a domain STAS (size 194) in uniprot entity S26A4_HUMAN there are 17 pathogenic changes around while only 4 benign (81%) in NM_000441.2
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC26A4NM_000441.2 linkc.2131G>T p.Asp711Tyr missense_variant Exon 19 of 21 ENST00000644269.2 NP_000432.1 O43511-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC26A4ENST00000644269.2 linkc.2131G>T p.Asp711Tyr missense_variant Exon 19 of 21 NM_000441.2 ENSP00000494017.1 O43511-1
SLC26A4ENST00000644846.1 linkn.*33G>T non_coding_transcript_exon_variant Exon 8 of 10 ENSP00000494344.1 A0A2R8Y4W7
SLC26A4ENST00000644846.1 linkn.*33G>T 3_prime_UTR_variant Exon 8 of 10 ENSP00000494344.1 A0A2R8Y4W7
SLC26A4ENST00000492030.2 linkn.377-60G>T intron_variant Intron 3 of 5 5

Frequencies

GnomAD3 genomes
AF:
0.000184
AC:
28
AN:
152182
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000675
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
GnomAD3 exomes
AF:
0.0000557
AC:
14
AN:
251272
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135794
show subpopulations
Gnomad AFR exome
AF:
0.000861
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000212
AC:
31
AN:
1459282
Hom.:
0
Cov.:
29
AF XY:
0.0000179
AC XY:
13
AN XY:
726184
show subpopulations
Gnomad4 AFR exome
AF:
0.000749
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:
0.00000360
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.000184
AC:
28
AN:
152300
Hom.:
0
Cov.:
32
AF XY:
0.000188
AC XY:
14
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.000673
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
Alfa
AF:
0.0000966
Hom.:
0
Bravo
AF:
0.000219
ESP6500AA
AF:
0.00136
AC:
6
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000988
AC:
12

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Jun 25, 2024
GeneDx
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Pathogenic
0.31
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.67
D;D
Eigen
Pathogenic
0.83
Eigen_PC
Pathogenic
0.81
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.87
.;D
M_CAP
Uncertain
0.16
D
MetaRNN
Uncertain
0.73
D;D
MetaSVM
Pathogenic
0.99
D
MutationAssessor
Benign
1.7
L;L
PrimateAI
Benign
0.48
T
PROVEAN
Pathogenic
-5.7
D;.
REVEL
Pathogenic
0.87
Sift
Uncertain
0.0020
D;.
Sift4G
Uncertain
0.0020
D;.
Polyphen
1.0
D;D
Vest4
0.75
MVP
1.0
MPC
0.075
ClinPred
0.46
T
GERP RS
5.5
Varity_R
0.92
gMVP
0.73

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

LitVar

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

Other links and lift over

dbSNP: rs145805875; hg19: chr7-107350540; API