6-25923697-T-G

Variant names:

• chr6-25923697-T-G
• rs964825162
• NM_001286123.3:c.238A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001286123.3(SLC17A2):​c.238A>C​(p.Lys80Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,612,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 19/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC17A2 NM_001286123.3 missense, splice_region
• Scores: Splicing: ADA: 0.0003360
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.845
• Publications: 0 publications found

Genes affected

SLC17A2 (HGNC:10930): (solute carrier family 17 member 2) Predicted to enable sialic acid transmembrane transporter activity. Predicted to be involved in sialic acid transport. Predicted to be located in membrane. Predicted to be active in lysosome. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.08583304).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286123.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC17A2	NM_001286123.3	MANE Select	c.238A>C	p.Lys80Gln	missense splice_region	Exon 3 of 12	NP_001273052.1	O00624-3
	SLC17A2	NM_005835.4		c.238A>C	p.Lys80Gln	missense splice_region	Exon 3 of 11	NP_005826.1	O00624-2
	SLC17A2	NM_001286125.2		c.238A>C	p.Lys80Gln	missense splice_region	Exon 2 of 10	NP_001273054.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC17A2	ENST00000377850.8	TSL:5 MANE Select	c.238A>C	p.Lys80Gln	missense splice_region	Exon 3 of 12	ENSP00000367081.3	O00624-3
	SLC17A2	ENST00000360488.7	TSL:1	c.238A>C	p.Lys80Gln	missense splice_region	Exon 3 of 11	ENSP00000353677.3	O00624-2
	SLC17A2	ENST00000882944.1		c.238A>C	p.Lys80Gln	missense splice_region	Exon 3 of 13	ENSP00000553003.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460580 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726656

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000598 AC: 2 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110902

Other (OTH) AF: 0.00 AC: 0 AN: 60344

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74372

African (AFR) AF: 0.0000241 AC: 1 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	3.5
DANN	Benign	0.83
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.11	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.67	N
PhyloP100		0.84
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.066
Sift	Benign	0.23	T
Sift4G	Benign	0.29	T
Polyphen		0.0090	B
Vest4		0.19
MutPred		0.51		Loss of ubiquitination at K80 (P = 0.0074)
MVP		0.22
MPC		0.23
ClinPred		0.11	T
GERP RS		2.4
Varity_R		0.052
gMVP		0.25
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00034
dbscSNV1_RF	Benign	0.012
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: rs964825162; hg19: chr6-25923925;