chr12-128808255-T-A

Variant names:

• chr12-128808255-T-A
• rs959987
• NM_145648.4:c.1258+533A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145648.4(SLC15A4):​c.1258+533A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC15A4 NM_145648.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98
• Publications: 10 publications found

Genes affected

SLC15A4 (HGNC:23090): (solute carrier family 15 member 4) Enables L-histidine transmembrane transporter activity; peptide transmembrane transporter activity; and peptidoglycan transmembrane transporter activity. Involved in several processes, including dipeptide import across plasma membrane; peptidoglycan transport; and positive regulation of toll-like receptor signaling pathway. Located in endolysosome membrane. Is integral component of lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145648.4. 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
	SLC15A4	NM_145648.4	MANE Select	c.1258+533A>T		intron	N/A	NP_663623.1	Q8N697-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC15A4	ENST00000266771.10	TSL:1 MANE Select	c.1258+533A>T		intron	N/A	ENSP00000266771.5	Q8N697-1
	SLC15A4	ENST00000923390.1		c.1408+533A>T		intron	N/A	ENSP00000593449.1
	SLC15A4	ENST00000964262.1		c.1234+533A>T		intron	N/A	ENSP00000634321.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.18
DANN	Benign	0.55
PhyloP100		-2.0

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: rs959987; hg19: chr12-129292800;