6-25819902-T-A

Variant summary

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

The NM_005074.5(SLC17A1):c.221A>T(p.Asn74Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC17A1 NM_005074.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.20

Genes affected

SLC17A1 (HGNC:10929): (solute carrier family 17 member 1) Predicted to enable sialic acid transmembrane transporter activity. Involved in urate metabolic process and urate transport. Located in apical plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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	UniProt
SLC17A1	NM_005074.5	c.221A>T	p.Asn74Ile	missense_variant	4/13	ENST00000244527.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC17A1	ENST00000244527.10	c.221A>T	p.Asn74Ile	missense_variant	4/13	5	NM_005074.5	P1
SLC17A1	ENST00000468082.1	c.221A>T	p.Asn74Ile	missense_variant	3/10	1
SLC17A1	ENST00000476801.5	c.221A>T	p.Asn74Ile	missense_variant	4/12	2		P1
SLC17A1	ENST00000377886.6	c.221A>T	p.Asn74Ile	missense_variant, NMD_transcript_variant	4/12	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Jun 29, 2023

The c.221A>T (p.N74I) alteration is located in exon 4 (coding exon 3) of the SLC17A1 gene. This alteration results from a A to T substitution at nucleotide position 221, causing the asparagine (N) at amino acid position 74 to be replaced by an isoleucine (I). 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	0.16
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
Cadd	Benign	22
Dann	Uncertain	0.98
DEOGEN2	Uncertain	0.48	T;T;.
Eigen	Benign	-0.040
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.26	N
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.4	M;M;M
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-5.8	D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		0.98	D;D;D
Vest4		0.51
MutPred		0.60		Gain of methylation at K69 (P = 0.0391);Gain of methylation at K69 (P = 0.0391);Gain of methylation at K69 (P = 0.0391);
MVP		0.78
MPC		0.54
ClinPred		0.99	D
GERP RS		3.1
Varity_R		0.68
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr6-25820130;