chr7-107710154-G-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 4P and 5B. PM1PM2BP4_StrongBP6
The NM_000441.2(SLC26A4):c.2190G>T(p.Gln730His) variant causes a missense change. The variant allele was found at a frequency of 0.000186 in 1,609,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00088 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
SLC26A4
NM_000441.2 missense
NM_000441.2 missense
Scores
6
12
Clinical Significance
Conservation
PhyloP100: 3.78
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_benign. Variant got -1 ACMG points.
PM1
?
In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 6 uncertain in NM_000441.2
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.009727389).
BP6
?
Variant 7-107710154-G-T is Benign according to our data. Variant chr7-107710154-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 43543.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=6, Benign=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC26A4 | NM_000441.2 | c.2190G>T | p.Gln730His | missense_variant | 19/21 | ENST00000644269.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC26A4 | ENST00000644269.2 | c.2190G>T | p.Gln730His | missense_variant | 19/21 | NM_000441.2 | P1 | ||
SLC26A4 | ENST00000644846.1 | c.*92G>T | 3_prime_UTR_variant, NMD_transcript_variant | 8/10 | |||||
SLC26A4 | ENST00000492030.2 | n.377-1G>T | splice_acceptor_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000881 AC: 134AN: 152144Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
134
AN:
152144
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000306 AC: 77AN: 251294Hom.: 1 AF XY: 0.000199 AC XY: 27AN XY: 135804
GnomAD3 exomes
AF:
AC:
77
AN:
251294
Hom.:
AF XY:
AC XY:
27
AN XY:
135804
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000113 AC: 165AN: 1457022Hom.: 0 Cov.: 27 AF XY: 0.000110 AC XY: 80AN XY: 725230
GnomAD4 exome
AF:
AC:
165
AN:
1457022
Hom.:
Cov.:
27
AF XY:
AC XY:
80
AN XY:
725230
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000880 AC: 134AN: 152262Hom.: 0 Cov.: 32 AF XY: 0.000765 AC XY: 57AN XY: 74466
GnomAD4 genome
?
AF:
AC:
134
AN:
152262
Hom.:
Cov.:
32
AF XY:
AC XY:
57
AN XY:
74466
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
11
ESP6500EA
AF:
AC:
1
ExAC
?
AF:
AC:
45
Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:8
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Pendred syndrome Uncertain:1Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 11, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Dec 07, 2017 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 25, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 04, 2012 | Gln730His in exon 19 of SLC26A4: This variant is not expected to have clinical s ignificance because it is has been identified in 0.3% (11/3738) of African Ameri can chromosomes from a broad population by the NHLBI Exome sequencing project (h ttp://evs.gs.washington.edu/EVS/; dbSNP rs142723249). - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 29, 2020 | Observed heterozygous in unrelated patients with hearing loss in published literature (Landa et al., 2013; Chen et al., 2011); This variant is associated with the following publications: (PMID: 30245029, 21704276, 23965030) - |
Autosomal recessive nonsyndromic hearing loss 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;.
REVEL
Uncertain
Sift
Benign
D;.
Sift4G
Benign
T;.
Polyphen
B;B
Vest4
MutPred
Loss of stability (P = 0.0717);Loss of stability (P = 0.0717);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at