Genetic Variant SLC26A4:p.Leu30Leu (chr7-107661731-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_000441.2(SLC26A4):c.90C>T(p.Leu30Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,403,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L30L) has been classified as Likely benign. The gene SLC26A4 is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

SLC26A4
NM_000441.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.163

Publications

0 publications found

Variant links:

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 links:

SLC26A4-AS1 (HGNC:22385): (SLC26A4 antisense RNA 1)

SLC26A4-AS1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000441.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Specifications for SLC26A4 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.22).

BP7

Synonymous conserved (PhyloP=0.163 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000441.2. 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
	SLC26A4	NM_000441.2	MANE Select	c.90C>T	p.Leu30Leu	synonymous	Exon 2 of 21	NP_000432.1	O43511-1
	SLC26A4-AS1	NR_028137.1		n.68G>A		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC26A4	ENST00000644269.2	MANE Select	c.90C>T	p.Leu30Leu	synonymous	Exon 2 of 21	ENSP00000494017.1	O43511-1
SLC26A4	ENST00000888701.1		c.90C>T	p.Leu30Leu	synonymous	Exon 1 of 20	ENSP00000558760.1
SLC26A4	ENST00000888700.1		c.90C>T	p.Leu30Leu	synonymous	Exon 2 of 20	ENSP00000558759.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.13e-7

AC:

AN:

1403182

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

693490

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32270

American (AMR)

AF:

0.00

AC:

AN:

37202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25280

East Asian (EAS)

AF:

0.00

AC:

AN:

36916

South Asian (SAS)

AF:

0.00

AC:

AN:

80080

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41756

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5524

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1085676

Other (OTH)

AF:

0.0000171

AC:

AN:

58478

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over