chr13-29517166-C-A

Variant names:

• chr13-29517166-C-A
• rs765191110
• NM_003045.5:c.1655G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_003045.5(SLC7A1):​c.1655G>T​(p.Ser552Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S552N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC7A1 NM_003045.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.04
• Publications: 0 publications found

Genes affected

SLC7A1 (HGNC:11057): (solute carrier family 7 member 1) Enables L-arginine transmembrane transporter activity and L-histidine transmembrane transporter activity. Involved in amino acid transport. Located in membrane. Part of apical plasma membrane; basolateral plasma membrane; and protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.847

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003045.5. 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
	SLC7A1	NM_003045.5	MANE Select	c.1655G>T	p.Ser552Ile	missense	Exon 11 of 13	NP_003036.1	P30825

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A1	ENST00000380752.10	TSL:1 MANE Select	c.1655G>T	p.Ser552Ile	missense	Exon 11 of 13	ENSP00000370128.5	P30825
	SLC7A1	ENST00000936269.1		c.1817G>T	p.Ser606Ile	missense	Exon 12 of 14	ENSP00000606328.1
	SLC7A1	ENST00000936271.1		c.1679G>T	p.Ser560Ile	missense	Exon 11 of 13	ENSP00000606330.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458234 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725100

⚠️ 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: 33400

American (AMR) AF: 0.00 AC: 0 AN: 44218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25844

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 85436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110480

Other (OTH) AF: 0.00 AC: 0 AN: 60228

⚠️ 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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.83	D
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.36	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	0.60	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		6.0
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Pathogenic	0.78
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.96	D
Vest4		0.83
MutPred		0.40		Loss of disorder (P = 5e-04)
MVP		0.84
MPC		1.6
ClinPred		0.99	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.82
gMVP		0.87
Mutation Taster		=7/93	disease causing

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: rs765191110; hg19: chr13-30091303;