chr7-123147170-C-G

Position:

• chr7-123147170-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_022444.4(SLC13A1):​c.801G>C​(p.Glu267Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E267K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC13A1 NM_022444.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28

Genes affected

SLC13A1 (HGNC:10916): (solute carrier family 13 member 1) The protein encoded by this gene is an apical membrane Na(+)-sulfate cotransporter involved in sulfate homeostasis in the kidney. Defects in this gene lead to many pathophysiologic problems. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.768

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC13A1	NM_022444.4	c.801G>C	p.Glu267Asp	missense_variant	7/15	ENST00000194130.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC13A1	ENST00000194130.7	c.801G>C	p.Glu267Asp	missense_variant	7/15	1	NM_022444.4	P1
SLC13A1	ENST00000439260.5	c.*1179G>C		3_prime_UTR_variant, NMD_transcript_variant	10/18	1
SLC13A1	ENST00000539873.1	c.*468G>C		3_prime_UTR_variant	8/16	5
SLC13A1	ENST00000427975.5	c.*744G>C		3_prime_UTR_variant, NMD_transcript_variant	8/16	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461224 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726912

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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

Dec 12, 2023

The c.801G>C (p.E267D) alteration is located in exon 7 (coding exon 7) of the SLC13A1 gene. This alteration results from a G to C substitution at nucleotide position 801, causing the glutamic acid (E) at amino acid position 267 to be replaced by an aspartic acid (D). 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	Benign	0.34
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.084	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.012	T
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.1	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.22
Sift	Benign	0.071	T
Sift4G	Benign	0.20	T
Polyphen		1.0	D
Vest4		0.71
MutPred		0.60		Loss of helix (P = 0.1299);
MVP		0.53
MPC		0.42
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.38
gMVP		0.75

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

LitVar

Other links and lift over

dbSNP: rs1794381426; hg19: chr7-122787224;