chr11-2918030-CC-TT

Variant names:

• chr11-2918030-CC-TT
• NM_002555.6:c.698_699delCCinsTT
• SLC67A1 p.Ser233Phe

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PS1

The NM_002555.6(SLC67A1):​c.698_699delCCinsTT​(p.Ser233Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Pathogenic in ClinVar.

• Frequency: Genomes: not found (cov: 36)
• Consequence: SLC67A1 NM_002555.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.371
• Publications: 0 publications found

Genes affected

SLC67A1 (HGNC:10964): (solute carrier family 22 member 18) This gene is one of several tumor-suppressing subtransferable fragments located in the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. This gene is imprinted, with preferential expression from the maternal allele. Mutations in this gene have been found in Wilms' tumor and lung cancer. This protein may act as a transporter of organic cations, and have a role in the transport of chloroquine and quinidine-related compounds in kidney. Several alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Oct 2015]

ACMG classification

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

• PS1: Transcript NM_002555.6 (SLC67A1) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002555.6. 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
	SLC67A1	NM_002555.6	MANE Select	c.698_699delCCinsTT	p.Ser233Phe	missense	N/A	NP_002546.3
	SLC67A1	NM_001315501.2		c.953_954delCCinsTT	p.Ser318Phe	missense	N/A	NP_001302430.1
	SLC67A1	NM_183233.3		c.698_699delCCinsTT	p.Ser233Phe	missense	N/A	NP_899056.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC67A1	ENST00000649076.2	MANE Select	c.698_699delCCinsTT	p.Ser233Phe	missense	N/A	ENSP00000497561.1	Q96BI1
	SLC67A1	ENST00000347936.6	TSL:1	c.698_699delCCinsTT	p.Ser233Phe	missense	N/A	ENSP00000307859.2	Q96BI1
	SLC67A1	ENST00000380574.5	TSL:1	c.698_699delCCinsTT	p.Ser233Phe	missense	N/A	ENSP00000369948.1	Q96BI1

Frequencies

GnomAD3 genomes Cov.: 36

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

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.37

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-2939260;