rs72655395

Variant names:

• chr7-103380593-G-A
• rs72655395
• NM_198999.3:c.1515-44C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198999.3(SLC26A5):​c.1515-44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00443 in 1,551,366 control chromosomes in the GnomAD database, including 248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (128 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (120 hom.)
• Consequence: SLC26A5 NM_198999.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.143
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 7-103380593-G-A is Benign according to our data. Variant chr7-103380593-G-A is described in ClinVar as Benign. ClinVar VariationId is 676192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.079 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198999.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A5	NM_198999.3	MANE Select	c.1515-44C>T		intron	N/A	NP_945350.1	P58743-1
	SLC26A5	NM_001167962.2		c.1419-44C>T		intron	N/A	NP_001161434.1	P58743-5
	SLC26A5	NM_206883.3		c.1515-44C>T		intron	N/A	NP_996766.1	P58743-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A5	ENST00000306312.8	TSL:1 MANE Select	c.1515-44C>T		intron	N/A	ENSP00000304783.3	P58743-1
	SLC26A5	ENST00000393727.5	TSL:1	c.1515-44C>T		intron	N/A	ENSP00000377328.1	Q7Z7F4
	SLC26A5	ENST00000393723.2	TSL:1	c.1419-44C>T		intron	N/A	ENSP00000377324.1	P58743-6

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 3506 AN: 151996 Hom.: 129 Cov.: 32

Gnomad AFR AF: 0.0811

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00694

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00619 AC: 1551 AN: 250544 AF XY: 0.00461

Gnomad AFR exome AF: 0.0851

Gnomad AMR exome AF: 0.00383

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.00213

GnomAD4 exome AF: 0.00240 AC: 3357 AN: 1399252 Hom.: 120 Cov.: 23 AF XY: 0.00207 AC XY: 1447 AN XY: 699680

African (AFR) AF: 0.0850 AC: 2733 AN: 32138

American (AMR) AF: 0.00417 AC: 186 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25742

East Asian (EAS) AF: 0.000102 AC: 4 AN: 39374

South Asian (SAS) AF: 0.000141 AC: 12 AN: 84940

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53260

Middle Eastern (MID) AF: 0.00284 AC: 16 AN: 5632

European-Non Finnish (NFE) AF: 0.0000967 AC: 102 AN: 1055288

Other (OTH) AF: 0.00522 AC: 304 AN: 58284

GnomAD4 genome AF: 0.0231 AC: 3521 AN: 152114 Hom.: 128 Cov.: 32 AF XY: 0.0225 AC XY: 1675 AN XY: 74376

African (AFR) AF: 0.0813 AC: 3368 AN: 41442

American (AMR) AF: 0.00693 AC: 106 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 67972

Other (OTH) AF: 0.0132 AC: 28 AN: 2114

Alfa AF: 0.0125 Hom.: 33

Bravo AF: 0.0257

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.56
PhyloP100		-0.14
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: rs72655395; hg19: chr7-103021040;