NM_198999.3:c.293-3361C>G

Variant names:

• chr7-103416473-G-C
• rs17142677
• NM_198999.3:c.293-3361C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107
• Publications: 2 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 -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	c.293-3361C>G		intron_variant	Intron 4 of 19	ENST00000306312.8	NP_945350.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15512 AN: 152170 Hom.: 895 Cov.: 32

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.: 32 AF XY: 0.104 AC XY: 7759 AN XY: 74456

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: 28 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7446 AN: 68018

Other (OTH) AF: 0.108 AC: 228 AN: 2116

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
DANN	Benign	0.34
PhyloP100		0.11
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: rs17142677; hg19: chr7-103056920;