NM_000441.2:c.-3-195C>A

Variant names:

• chr7-107661444-C-A
• rs55706020
• NM_000441.2:c.-3-195C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000441.2(SLC26A4):​c.-3-195C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: SLC26A4 NM_000441.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250
• Publications: 0 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-AS1 (HGNC:22385): (SLC26A4 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).

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.-3-195C>A		intron	N/A	NP_000432.1	O43511-1
	SLC26A4-AS1	NR_028137.1		n.197+158G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A4	ENST00000644269.2	MANE Select	c.-3-195C>A		intron	N/A	ENSP00000494017.1	O43511-1
	SLC26A4	ENST00000888701.1		c.-198C>A		5_prime_UTR	Exon 1 of 20	ENSP00000558760.1
	SLC26A4	ENST00000888700.1		c.-3-195C>A		intron	N/A	ENSP00000558759.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 5

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.5
DANN	Benign	0.44
PhyloP100		-0.25
PromoterAI		-0.013	Neutral

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: rs55706020; hg19: chr7-107301889;