chr7-107710179-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_000441.2(SLC26A4):​c.2215C>G​(p.Gln739Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q739Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

SLC26A4
NM_000441.2 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.40

Publications

2 publications found
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]
SLC26A4 Gene-Disease associations (from GenCC):
  • autosomal recessive nonsyndromic hearing loss 4
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
  • Pendred syndrome
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
  • athyreosis
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • thyroid hypoplasia
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • hearing loss, autosomal recessive
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 167 curated pathogenic missense variants (we use a threshold of 10). The gene has 19 curated benign missense variants. Trascript score misZ: -1.7621 (below the threshold of 3.09). GenCC associations: The gene is linked to autosomal recessive nonsyndromic hearing loss 4, Pendred syndrome, athyreosis, thyroid hypoplasia, hearing loss, autosomal recessive.
BP4
Computational evidence support a benign effect (MetaRNN=0.19435802).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC26A4NM_000441.2 linkc.2215C>G p.Gln739Glu 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.2215C>G p.Gln739Glu missense_variant Exon 19 of 21 NM_000441.2 ENSP00000494017.1 O43511-1
SLC26A4ENST00000492030.2 linkn.401C>G non_coding_transcript_exon_variant Exon 4 of 6 5
SLC26A4ENST00000644846.1 linkn.*117C>G non_coding_transcript_exon_variant Exon 8 of 10 ENSP00000494344.1 A0A2R8Y4W7
SLC26A4ENST00000644846.1 linkn.*117C>G 3_prime_UTR_variant Exon 8 of 10 ENSP00000494344.1 A0A2R8Y4W7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
27
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.060
BayesDel_addAF
Uncertain
0.026
T
BayesDel_noAF
Benign
-0.20
CADD
Benign
17
DANN
Benign
0.95
DEOGEN2
Benign
0.082
T;T
Eigen
Benign
-0.47
Eigen_PC
Benign
-0.24
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.65
.;T
M_CAP
Benign
0.052
D
MetaRNN
Benign
0.19
T;T
MetaSVM
Uncertain
-0.12
T
MutationAssessor
Benign
0.90
L;L
PhyloP100
2.4
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.040
N;.
REVEL
Benign
0.23
Sift
Benign
0.29
T;.
Sift4G
Benign
0.76
T;.
Polyphen
0.0
B;B
Vest4
0.35
MutPred
0.34
Loss of loop (P = 0.0112);Loss of loop (P = 0.0112);
MVP
0.92
MPC
0.011
ClinPred
0.28
T
GERP RS
4.6
Varity_R
0.11
gMVP
0.53
Mutation Taster
=74/26
polymorphism

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

Other links and lift over

dbSNP: rs727503431; hg19: chr7-107350624; API