7-107698067-A-G

Variant names:

• chr7-107698067-A-G
• NM_000441.2:c.1570A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1 PM2 BP4_Strong

The NM_000441.2(SLC26A4):​c.1570A>G​(p.Ile524Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,458,488 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: 0.0000055 (0 hom.)
• Consequence: SLC26A4 NM_000441.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.529

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 0 ACMG points.

• PM1: In a topological_domain Cytoplasmic (size 272) in uniprot entity S26A4_HUMAN there are 26 pathogenic changes around while only 8 benign (76%) in NM_000441.2
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057449043).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A4	NM_000441.2	c.1570A>G	p.Ile524Val	missense_variant	Exon 14 of 21	ENST00000644269.2	NP_000432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A4	ENST00000644269.2	c.1570A>G	p.Ile524Val	missense_variant	Exon 14 of 21		NM_000441.2	ENSP00000494017.1
SLC26A4	ENST00000477350.5	n.417A>G		non_coding_transcript_exon_variant	Exon 4 of 5	4
SLC26A4	ENST00000480841.5	n.419A>G		non_coding_transcript_exon_variant	Exon 5 of 8	3
SLC26A4	ENST00000644846.1	n.280A>G		non_coding_transcript_exon_variant	Exon 4 of 10			ENSP00000494344.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000549 AC: 8 AN: 1458488 Hom.: 0 Cov.: 28 AF XY: 0.00000551 AC XY: 4 AN XY: 725872

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: 0.00000721

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	0.080
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	12
DANN	Benign	0.66
DEOGEN2	Benign	0.079	T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.70	.;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.057	T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.035	N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.0	N;.
REVEL	Benign	0.22
Sift	Benign	0.89	T;.
Sift4G	Benign	1.0	T;.
Polyphen		0.0	B;B
Vest4		0.31
MutPred		0.46		Gain of disorder (P = 0.2025);Gain of disorder (P = 0.2025);
MVP		0.80
MPC		0.011
ClinPred		0.054	T
GERP RS		0.90
Varity_R		0.018
gMVP		0.43

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: chr7-107338512;