chr7-107701159-A-G

Variant names:

• chr7-107701159-A-G
• NM_000441.2:c.1766A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_000441.2(SLC26A4):​c.1766A>G​(p.Gln589Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 6.9e-7 (0 hom.)
• Consequence: SLC26A4 NM_000441.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.47

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 Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a domain STAS (size 194) in uniprot entity S26A4_HUMAN there are 17 pathogenic changes around while only 4 benign (81%) in NM_000441.2
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18269235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A4	NM_000441.2	c.1766A>G	p.Gln589Arg	missense_variant	Exon 16 of 21	ENST00000644269.2	NP_000432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A4	ENST00000644269.2	c.1766A>G	p.Gln589Arg	missense_variant	Exon 16 of 21		NM_000441.2	ENSP00000494017.1
SLC26A4	ENST00000480841.5	n.615A>G		non_coding_transcript_exon_variant	Exon 7 of 8	3
SLC26A4	ENST00000644846.1	n.476A>G		non_coding_transcript_exon_variant	Exon 6 of 10			ENSP00000494344.1
SLC26A4	ENST00000492030.2	n.91-668A>G		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457634 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 725532

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	0.12
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	18
DANN	Benign	0.60
DEOGEN2	Benign	0.17	T;T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.026
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	.;D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Uncertain	-0.073	T
MutationAssessor	Benign	0.62	N;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.10	N;.
REVEL	Benign	0.22
Sift	Benign	0.88	T;.
Sift4G	Benign	0.99	T;.
Polyphen		0.0	B;B
Vest4		0.40
MutPred		0.34		Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);
MVP		0.94
MPC		0.011
ClinPred		0.89	D
GERP RS		4.6
Varity_R		0.19
gMVP		0.63

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: chr7-107341604;