Did you swap ALT and REF sequences? Given REF is incompatible with our reference (hg38) sequence.

17-252338-A-G

Variant names:

• chr17-252338-A-G
• NM_006987.4:c.439-5053T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006987.4(RPH3AL):​c.439-5053T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: RPH3AL NM_006987.4 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0580

Genes affected

RPH3AL (HGNC:10296): (rabphilin 3A like (without C2 domains)) The protein encoded by this gene plays a direct regulatory role in calcium-ion-dependent exocytosis in both endocrine and exocrine cells and plays a key role in insulin secretion by pancreatic cells. This gene is likely a tumor suppressor. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPH3AL	NM_006987.4	c.439-5053T>C		intron_variant	Intron 6 of 9	ENST00000331302.12	NP_008918.1
RPH3AL	NM_001190411.2	c.439-5053T>C		intron_variant	Intron 5 of 8		NP_001177340.1
RPH3AL	NM_001190412.2	c.352-5053T>C		intron_variant	Intron 5 of 8		NP_001177341.1
RPH3AL	NM_001190413.2	c.352-5053T>C		intron_variant	Intron 4 of 7		NP_001177342.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPH3AL	ENST00000331302.12	c.439-5053T>C		intron_variant	Intron 6 of 9	2	NM_006987.4	ENSP00000328977.7

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 01, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.44T>C (p.M15T) alteration is located in exon 1 (coding exon 1) of the CCL3L1 gene. This alteration results from a T to C substitution at nucleotide position 44, causing the methionine (M) at amino acid position 15 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-102129;