NM_022444.4:c.521A>T

Variant names:

• chr7-123169180-T-A
• rs2140516
• NM_022444.4:c.521A>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/22 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)
• Consequence: SLC13A1 NM_022444.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369
• Publications: 40 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022444.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC13A1	NM_022444.4	MANE Select	c.521A>T	p.Asn174Ile	missense	Exon 4 of 15	NP_071889.2
	SLC13A1	NM_001324400.1		c.-197A>T		5_prime_UTR	Exon 5 of 18	NP_001311329.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC13A1	ENST00000194130.7	TSL:1 MANE Select	c.521A>T	p.Asn174Ile	missense	Exon 4 of 15	ENSP00000194130.2
	SLC13A1	ENST00000439260.5	TSL:1	n.*554A>T		non_coding_transcript_exon	Exon 5 of 18	ENSP00000401417.1
	SLC13A1	ENST00000439260.5	TSL:1	n.*554A>T		3_prime_UTR	Exon 5 of 18	ENSP00000401417.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.37
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.056
Sift	Uncertain	0.021	D
Sift4G	Benign	0.065	T
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
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs2140516; hg19: chr7-122809234;