17-213884-C-T

Variant names:

• chr17-213884-C-T
• NM_006987.4:c.916G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006987.4(RPH3AL):​c.916G>A​(p.Ala306Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: RPH3AL NM_006987.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09804627).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPH3AL	NM_006987.4	c.916G>A	p.Ala306Thr	missense_variant	Exon 10 of 10	ENST00000331302.12	NP_008918.1
RPH3AL	NM_001190411.2	c.916G>A	p.Ala306Thr	missense_variant	Exon 9 of 9		NP_001177340.1
RPH3AL	NM_001190412.2	c.829G>A	p.Ala277Thr	missense_variant	Exon 9 of 9		NP_001177341.1
RPH3AL	NM_001190413.2	c.829G>A	p.Ala277Thr	missense_variant	Exon 8 of 8		NP_001177342.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPH3AL	ENST00000331302.12	c.916G>A	p.Ala306Thr	missense_variant	Exon 10 of 10	2	NM_006987.4	ENSP00000328977.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461424 Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7 AN XY: 727010

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T;T;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.46	T;.;.;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.098	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.31	.;.;N;N
REVEL	Benign	0.018
Sift	Benign	0.13	.;.;T;D
Sift4G	Benign	0.57	T;T;T;T
Polyphen		0.0060	B;B;B;B
Vest4		0.083
MutPred		0.16		Gain of phosphorylation at A306 (P = 0.0024);Gain of phosphorylation at A306 (P = 0.0024);.;.;
MVP		0.15
MPC		0.058
ClinPred		0.054	T
GERP RS		2.1
Varity_R		0.068
gMVP		0.12

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-63675;