7-107694650-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate

The NM_000441.2(SLC26A4):ā€‹c.1371C>Gā€‹(p.Asn457Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

SLC26A4
NM_000441.2 missense

Scores

11
7
1

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 2.82
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 Likely_pathogenic. Variant got 8 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.979
PP5
Variant 7-107694650-C-G is Pathogenic according to our data. Variant chr7-107694650-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1064655.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC26A4NM_000441.2 linkuse as main transcriptc.1371C>G p.Asn457Lys missense_variant 12/21 ENST00000644269.2 NP_000432.1 O43511-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC26A4ENST00000644269.2 linkuse as main transcriptc.1371C>G p.Asn457Lys missense_variant 12/21 NM_000441.2 ENSP00000494017.1 O43511-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461340
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727002
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Autosomal recessive nonsyndromic hearing loss 4 Pathogenic:1
Likely pathogenic, criteria provided, single submitterclinical testingNeurogenetic Laboratory, Second Faculty of Medicine, Charles UniversityMar 30, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.060
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.89
D;D
Eigen
Pathogenic
0.82
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.94
.;D
M_CAP
Uncertain
0.26
D
MetaRNN
Pathogenic
0.98
D;D
MetaSVM
Pathogenic
1.0
D
MutationAssessor
Pathogenic
3.3
M;M
PrimateAI
Uncertain
0.70
T
PROVEAN
Pathogenic
-6.0
D;.
REVEL
Pathogenic
0.78
Sift
Pathogenic
0.0
D;.
Sift4G
Uncertain
0.0020
D;.
Polyphen
1.0
D;D
Vest4
0.94
MutPred
0.92
Gain of ubiquitination at N457 (P = 0.0267);Gain of ubiquitination at N457 (P = 0.0267);
MVP
1.0
MPC
0.076
ClinPred
1.0
D
GERP RS
5.5
Varity_R
0.97
gMVP
0.83

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-107335095; API