NM_006987.4:c.*1672C>T

Variant names:

• chr17-212180-G-A
• rs11650641
• NM_006987.4:c.*1672C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006987.4(RPH3AL):​c.*1672C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 152,294 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.

• Frequency: Genomes: 𝑓 0.0019 (0 hom., cov: 33)
• Consequence: RPH3AL NM_006987.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPH3AL	NM_006987.4	c.*1672C>T		downstream_gene_variant		ENST00000331302.12	NP_008918.1
RPH3AL	NM_001190411.2	c.*1672C>T		downstream_gene_variant			NP_001177340.1
RPH3AL	NM_001190412.2	c.*1672C>T		downstream_gene_variant			NP_001177341.1
RPH3AL	NM_001190413.2	c.*1672C>T		downstream_gene_variant			NP_001177342.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPH3AL	ENST00000331302.12	c.*1672C>T		downstream_gene_variant		2	NM_006987.4	ENSP00000328977.7
RPH3AL	ENST00000618002.4	c.*1672C>T		downstream_gene_variant		5		ENSP00000479485.1

Frequencies

GnomAD3 genomes AF: 0.00188 AC: 286 AN: 152176 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000628

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00326

Gnomad OTH AF: 0.00287

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

GnomAD4 genome AF: 0.00187 AC: 285 AN: 152294 Hom.: 0 Cov.: 33 AF XY: 0.00199 AC XY: 148 AN XY: 74480

Gnomad4 AFR AF: 0.000626

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00326

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00312 Hom.: 0

Bravo AF: 0.00211

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11650641; hg19: chr17-61971;