5-140366235-C-G

Position:

• chr5-140366235-C-G

Variant summary

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

The ENST00000506757.7(SLC4A9):​c.1984C>G​(p.Pro662Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,449,208 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC4A9 ENST00000506757.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.10

Genes affected

SLC4A9 (HGNC:11035): (solute carrier family 4 member 9) The protein encoded by this gene is a membrane protein involved in anion exchange. Expression of this gene is mostly limited to the kidney. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A9	NM_031467.3	c.1984C>G	p.Pro662Ala	missense_variant	14/22	ENST00000506757.7	NP_113655.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A9	ENST00000506757.7	c.1984C>G	p.Pro662Ala	missense_variant	14/22	1	NM_031467.3	ENSP00000424424	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449208 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 719950

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: 9.05e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2022

The c.1984C>G (p.P662A) alteration is located in exon 14 (coding exon 14) of the SLC4A9 gene. This alteration results from a C to G substitution at nucleotide position 1984, causing the proline (P) at amino acid position 662 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.73	.;.;.;D
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.64	D;D;D;D
MetaSVM	Uncertain	0.42	D
MutationAssessor	Uncertain	2.6	.;.;.;M
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-6.8	D;D;D;D
REVEL	Uncertain	0.59
Sift	Uncertain	0.014	D;D;D;D
Sift4G	Uncertain	0.0090	D;D;D;D
Polyphen		1.0	D;.;D;D
Vest4		0.49
MutPred		0.67		.;.;.;Loss of stability (P = 0.0437);
MVP		0.87
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.60
gMVP		0.58

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: chr5-139745820;