6-25826555-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_005074.5(SLC17A1):c.113C>T(p.Ala38Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000183 in 1,611,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: SLC17A1 NM_005074.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.98

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.010516465).
• BP6: Variant 6-25826555-G-A is Benign according to our data. Variant chr6-25826555-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3163159.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC17A1	NM_005074.5	c.113C>T	p.Ala38Val	missense_variant	3/13	ENST00000244527.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC17A1	ENST00000244527.10	c.113C>T	p.Ala38Val	missense_variant	3/13	5	NM_005074.5	P1
SLC17A1	ENST00000468082.1	c.113C>T	p.Ala38Val	missense_variant	2/10	1
SLC17A1	ENST00000476801.5	c.113C>T	p.Ala38Val	missense_variant	3/12	2		P1
SLC17A1	ENST00000377886.6	c.113C>T	p.Ala38Val	missense_variant, NMD_transcript_variant	3/12	5

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 44 AN: 152050 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.000296 AC: 74 AN: 250052 Hom.: 0 AF XY: 0.000355 AC XY: 48 AN XY: 135130

Gnomad AFR exome AF: 0.0000620

Gnomad AMR exome AF: 0.000233

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.000623

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000327

Gnomad OTH exome AF: 0.000822

GnomAD4 exome AF: 0.000172 AC: 251 AN: 1459740 Hom.: 0 Cov.: 30 AF XY: 0.000201 AC XY: 146 AN XY: 726224

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000523

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000140

Gnomad4 OTH exome AF: 0.000216

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.000255 AC XY: 19 AN XY: 74412

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000353 Hom.: 0

Bravo AF: 0.000310

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000288 AC: 35

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000439

EpiControl AF: 0.000595

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.72
Cadd	Benign	0.035
Dann	Benign	0.11
DEOGEN2	Benign	0.054	T;T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0022	N
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.011	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.7	N;N;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	1.2	N;N;N
REVEL	Benign	0.094
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0050	B;B;B
Vest4		0.052
MVP		0.14
MPC		0.095
ClinPred		0.027	T
GERP RS		-6.6
Varity_R		0.022
gMVP		0.087

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: rs147069707; hg19: chr6-25826783;