8-17543321-G-T

Variant names:

• chr8-17543321-G-T
• rs114541623
• ENST00000004531.14:c.102G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001164771.2(SLC7A2):​c.102G>T​(p.Ser34Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S34S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC7A2 NM_001164771.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500
• Publications: 0 publications found

Genes affected

SLC7A2 (HGNC:11060): (solute carrier family 7 member 2) The protein encoded by this gene is a cationic amino acid transporter and a member of the APC (amino acid-polyamine-organocation) family of transporters. The encoded membrane protein is responsible for the cellular uptake of arginine, lysine and ornithine. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=0.05 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164771.2. 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
	SLC7A2	NM_001370338.1	MANE Select	c.-19G>T		5_prime_UTR	Exon 3 of 13	NP_001357267.1	P52569-1
	SLC7A2	NM_001164771.2		c.102G>T	p.Ser34Ser	synonymous	Exon 2 of 12	NP_001158243.1	P52569-3
	SLC7A2	NM_003046.6		c.102G>T	p.Ser34Ser	synonymous	Exon 2 of 12	NP_003037.4	P52569-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A2	ENST00000004531.14	TSL:1	c.102G>T	p.Ser34Ser	synonymous	Exon 2 of 12	ENSP00000004531.10	P52569-3
	SLC7A2	ENST00000398090.3	TSL:1	c.102G>T	p.Ser34Ser	synonymous	Exon 2 of 12	ENSP00000381164.3	P52569-2
	SLC7A2	ENST00000494857.6	TSL:5 MANE Select	c.-19G>T		5_prime_UTR	Exon 3 of 13	ENSP00000419140.2	P52569-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447516 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 718806

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

African (AFR) AF: 0.00 AC: 0 AN: 33036

American (AMR) AF: 0.00 AC: 0 AN: 42682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24892

East Asian (EAS) AF: 0.00 AC: 0 AN: 39588

South Asian (SAS) AF: 0.00 AC: 0 AN: 83664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53016

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1105190

Other (OTH) AF: 0.00 AC: 0 AN: 59772

⚠️ 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 Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.6
DANN	Benign	0.56
PhyloP100		0.050
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs114541623; hg19: chr8-17400830;