chr7-123169180-T-A

Position:

• chr7-123169180-T-A

Variant summary

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

The NM_022444.4(SLC13A1):​c.521A>T​(p.Asn174Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N174S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC13A1 NM_022444.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24938986).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC13A1	NM_022444.4	c.521A>T	p.Asn174Ile	missense_variant	4/15	ENST00000194130.7	NP_071889.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC13A1	ENST00000194130.7	c.521A>T	p.Asn174Ile	missense_variant	4/15	1	NM_022444.4	ENSP00000194130	P1
SLC13A1	ENST00000439260.5	c.*554A>T		3_prime_UTR_variant, NMD_transcript_variant	5/18	1		ENSP00000401417
SLC13A1	ENST00000539873.1	c.329A>T	p.Asn110Ile	missense_variant	3/16	5		ENSP00000441309
SLC13A1	ENST00000427975.5	c.*464A>T		3_prime_UTR_variant, NMD_transcript_variant	5/16	5		ENSP00000388403

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.17	T;.
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.71	T;T
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.4	M;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.056
Sift	Uncertain	0.021	D;T
Sift4G	Benign	0.065	T;D
Polyphen		0.54	P;.
Vest4		0.27
MutPred		0.53		Loss of disorder (P = 0.0419);.;
MVP		0.49
MPC		0.22
ClinPred		0.80	D
GERP RS		-4.7
Varity_R		0.16
gMVP		0.48

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: rs2140516; hg19: chr7-122809234;