rs72655388

Variant names:

• chr7-103391330-T-C
• rs72655388
• NM_198999.3:c.1233+292A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198999.3(SLC26A5):​c.1233+292A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0668 in 152,312 control chromosomes in the GnomAD database, including 1,124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.067 (1124 hom., cov: 32)
• Consequence: SLC26A5 NM_198999.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.73
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-103391330-T-C is Benign according to our data. Variant chr7-103391330-T-C is described in ClinVar as Benign. ClinVar VariationId is 1260262.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A5	NM_198999.3	c.1233+292A>G		intron_variant	Intron 11 of 19	ENST00000306312.8	NP_945350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A5	ENST00000306312.8	c.1233+292A>G		intron_variant	Intron 11 of 19	1	NM_198999.3	ENSP00000304783.3
SLC26A5	ENST00000393727.5	c.1233+292A>G		intron_variant	Intron 9 of 17	1		ENSP00000377328.1
SLC26A5	ENST00000393723.2	c.1233+292A>G		intron_variant	Intron 9 of 16	1		ENSP00000377324.1

Frequencies

GnomAD3 genomes AF: 0.0666 AC: 10132 AN: 152194 Hom.: 1117 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000764

Gnomad OTH AF: 0.0416

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

GnomAD4 genome AF: 0.0668 AC: 10179 AN: 152312 Hom.: 1124 Cov.: 32 AF XY: 0.0653 AC XY: 4865 AN XY: 74468

African (AFR) AF: 0.232 AC: 9641 AN: 41538

American (AMR) AF: 0.0254 AC: 389 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10628

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000764 AC: 52 AN: 68030

Other (OTH) AF: 0.0412 AC: 87 AN: 2114

Alfa AF: 0.0484 Hom.: 75

Bravo AF: 0.0760

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0030
DANN	Benign	0.35
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs72655388; hg19: chr7-103031777;