chr7-123169180-T-G

Variant names:

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

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>C​(p.Asn174Thr) 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. 16/22 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=0.0950194).

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>C	p.Asn174Thr	missense	Exon 4 of 15	NP_071889.2
	SLC13A1	NM_001324400.1		c.-197A>C		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>C	p.Asn174Thr	missense	Exon 4 of 15	ENSP00000194130.2
	SLC13A1	ENST00000439260.5	TSL:1	n.*554A>C		non_coding_transcript_exon	Exon 5 of 18	ENSP00000401417.1
	SLC13A1	ENST00000439260.5	TSL:1	n.*554A>C		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	0.062
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	2.5
DANN	Benign	0.67
DEOGEN2	Benign	0.072	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.37
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.0060
Sift	Benign	0.25	T
Sift4G	Benign	0.39	T
Polyphen		0.013	B
Vest4		0.17
MutPred		0.41		Loss of helix (P = 0.1299)
MVP		0.26
MPC		0.082
ClinPred		0.18	T
GERP RS		-4.7
Varity_R		0.053
gMVP		0.25
Mutation Taster		=87/13	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;