7-107694438-C-T

Variant names:

• chr7-107694438-C-T
• rs397516415
• NM_000441.2:c.1299C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_000441.2(SLC26A4):​c.1299C>T​(p.Ile433Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: SLC26A4 NM_000441.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.351
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 7-107694438-C-T is Benign according to our data. Variant chr7-107694438-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 43502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.351 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A4	NM_000441.2	c.1299C>T	p.Ile433Ile	synonymous_variant	Exon 11 of 21	ENST00000644269.2	NP_000432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A4	ENST00000644269.2	c.1299C>T	p.Ile433Ile	synonymous_variant	Exon 11 of 21		NM_000441.2	ENSP00000494017.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250884 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461362 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 727006

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111622

Other (OTH) AF: 0.0000166 AC: 1 AN: 60358

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jun 15, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Ile433Ile in exon 11 of SLC26A4: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence.

not provided Benign:1

Jun 21, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely 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	-0.36
CADD	Benign	5.1
DANN	Benign	0.84
PhyloP100		-0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs397516415; hg19: chr7-107334883;