rs111033240

Variant names:

• chr7-107663331-C-A
• NM_000441.2:c.200C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-107663331-C-A
• chr7-107663331-C-G
• chr7-107663331-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000441.2(SLC26A4):​c.200C>A​(p.Thr67Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC26A4 NM_000441.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.651

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06294361).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A4	NM_000441.2	c.200C>A	p.Thr67Asn	missense_variant	Exon 3 of 21	ENST00000644269.2	NP_000432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A4	ENST00000644269.2	c.200C>A	p.Thr67Asn	missense_variant	Exon 3 of 21		NM_000441.2	ENSP00000494017.1
SLC26A4	ENST00000440056.1	c.200C>A	p.Thr67Asn	missense_variant	Exon 3 of 4	4		ENSP00000394760.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	11
DANN	Benign	0.77
DEOGEN2	Benign	0.071	T;T;T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.56	.;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.063	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.6	L;L;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.36	N;.;N
REVEL	Benign	0.092
Sift	Benign	0.18	T;.;T
Sift4G	Benign	0.069	T;.;T
Polyphen		0.0010	B;B;.
Vest4		0.38
MutPred		0.47		Gain of ubiquitination at K66 (P = 0.115);Gain of ubiquitination at K66 (P = 0.115);Gain of ubiquitination at K66 (P = 0.115);
MVP		0.82
MPC		0.012
ClinPred		0.024	T
GERP RS		2.2
Varity_R		0.044
gMVP		0.53

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-107303776;