dbSNP rs17142677: SLC26A5:c.293-3361C>G (chr7-103416473-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_198999.3(SLC26A5):c.293-3361C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,290 control chromosomes in the GnomAD database, including 897 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.10 ( 897 hom., cov: 32)

Consequence

SLC26A5
NM_198999.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.107

Publications

2 publications found

Variant links:

Genes affected

SLC26A5 (HGNC:9359): (solute carrier family 26 member 5) This gene encodes a member of the SLC26A/SulP transporter family. The protein functions as a molecular motor in motile outer hair cells (OHCs) of the cochlea, inducing changes in cell length that act to amplify sound levels. The transmembrane protein is an incomplete anion transporter, and does not allow anions to cross the cell membrane but instead undergoes a conformational change in response to changes in intracellular Cl- levels that results in a change in cell length. The protein functions at microsecond rates, which is several orders of magnitude faster than conventional molecular motor proteins. Mutations in this gene are potential candidates for causing neurosensory deafness. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2009]

SLC26A5 Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 61
Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
nonsyndromic genetic hearing loss
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

SLC26A5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A5	NM_198999.3 link	c.293-3361C>G		intron_variant	Intron 4 of 19	ENST00000306312.8	NP_945350.1	P58743-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC26A5	ENST00000306312.8 link	c.293-3361C>G	intron_variant	Intron 4 of 19	1	NM_198999.3	ENSP00000304783.3	P58743-1
SLC26A5	ENST00000393727.5 link	c.293-3361C>G	intron_variant	Intron 2 of 17	1		ENSP00000377328.1	Q7Z7F4
SLC26A5	ENST00000393723.2 link	c.293-3361C>G	intron_variant	Intron 2 of 16	1		ENSP00000377324.1	P58743-6

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15512

AN:

152170

Hom.:

895

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0502

Gnomad AMI

AF:

0.160

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.193

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.0881

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.102

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.102

AC:

15527

AN:

152290

Hom.:

897

Cov.:

AF XY:

0.104

AC XY:

7759

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0503

AC:

2093

AN:

41582

American (AMR)

AF:

0.160

AC:

2451

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

418

AN:

3470

East Asian (EAS)

AF:

0.193

AC:

999

AN:

5174

South Asian (SAS)

AF:

0.162

AC:

784

AN:

4830

European-Finnish (FIN)

AF:

0.0881

AC:

934

AN:

10600

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.109

AC:

7446

AN:

68018

Other (OTH)

AF:

0.108

AC:

228

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

729

1458

2186

2915

3644

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

178

356

534

712

890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.106

Hom.:

115

Bravo

AF:

0.106

Asia WGS

AF:

0.208

AC:

722

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.8

(source)

DANN

Benign

0.34

PhyloP100

0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over