1-205915146-T-A

Position:

• chr1-205915146-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000367135(SLC26A9):​c.*211A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,840 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.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: SLC26A9 ENST00000367135 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.509

Genes affected

SLC26A9 (HGNC:14469): (solute carrier family 26 member 9) This gene is one member of a family of sulfate/anion transporter genes. Family members are well conserved in their genomic (number and size of exons) and protein (aa length among species) structures yet have markedly different tissue expression patterns. The product of this gene is a highly selective chloride ion channel regulated by WNK kinases. Alternative splicing results in multiple transcript variants encoding differing isoforms.[provided by RefSeq, Dec 2008]

SLC26A9 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09412363).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A9	NM_052934.4	c.*211A>T		3_prime_UTR_variant	21/21	ENST00000367135.8	NP_443166.1
SLC26A9	NM_134325.3	c.2410A>T	p.Arg804Trp	missense_variant	22/22		NP_599152.2
SLC26A9	XM_011509121.3	c.*211A>T		3_prime_UTR_variant	20/20		XP_011507423.1
SLC26A9	XM_011509122.3	c.*211A>T		3_prime_UTR_variant	18/18		XP_011507424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A9	ENST00000340781.8	c.2410A>T	p.Arg804Trp	missense_variant	21/21	1		ENSP00000341682.4
SLC26A9	ENST00000367135	c.*211A>T		3_prime_UTR_variant	21/21	1	NM_052934.4	ENSP00000356103.3
SLC26A9	ENST00000367134.2	c.2410A>T	p.Arg804Trp	missense_variant	22/22	5		ENSP00000356102.2
SLC26A9	ENST00000491127.5	n.1971A>T		non_coding_transcript_exon_variant	13/13	2

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151840 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151840 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74148

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	8.9
DANN	Benign	0.97
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.60	.;T
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.094	T;T
MetaSVM	Uncertain	-0.12	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.020	N;N
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0090	D;D
Vest4		0.15
MutPred		0.32		Loss of disorder (P = 0.0094);Loss of disorder (P = 0.0094);
MVP		0.32
MPC		0.19
ClinPred		0.91	D
GERP RS		0.71
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6669481; hg19: chr1-205884274;