1-231337292-C-T

Variant names:

• chr1-231337292-C-T
• rs758461827
• ENST00000391858:c.-1092C>T

Variant summary

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

The ENST00000391858(SPRTN):​c.-1092C>T variant causes a 5 prime UTR premature start codon gain 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: 32)
• Consequence: SPRTN ENST00000391858 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.666

Genes affected

SPRTN (HGNC:25356): (SprT-like N-terminal domain) The protein encoded by this gene may play a role in DNA repair during replication of damaged DNA. This protein recruits valosin containing protein (p97) to stalled DNA replication forks where it may prevent excessive translesional DNA synthesis and limit the number of DNA-damage induced mutations. It may also be involved in replication-related G2/M-checkpoint regulation. Deficiency of a similar protein in mouse causes chromosomal instability and progeroid phenotypes. Mutations in this gene have been associated with Ruijs-Aalfs syndrome (RJALS). Alternatively spliced transcript variants have been identified. [provided by RefSeq, Mar 2015]

EXOC8 (HGNC:24659): (exocyst complex component 8) This gene encodes a component of the exocyst complex, an evolutionarily conserved multi-protein complex that plays a critical role in vesicular trafficking and the secretory pathway by targeting post-Golgi vesicles to the plasma membrane. This protein is a target of activated Ral subfamily of GTPases and thereby regulates exocytosis by tethering vesicles to the plasma membrane. Mutations in this gene may be related to Joubert syndrome. [provided by RefSeq, Sep 2016]

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=0.06820333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC8	NM_175876.5	c.454G>A	p.Gly152Ser	missense_variant	Exon 1 of 1	ENST00000366645.1	NP_787072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPRTN	ENST00000391858	c.-1092C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	1		ENSP00000375731.4
EXOC8	ENST00000366645.1	c.454G>A	p.Gly152Ser	missense_variant	Exon 1 of 1	6	NM_175876.5	ENSP00000355605.2
SPRTN	ENST00000391858	c.-1092C>T		5_prime_UTR_variant	Exon 1 of 4	1		ENSP00000375731.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	16
DANN	Benign	0.90
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PrimateAI	Uncertain	0.49	T
REVEL	Benign	0.072
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.33		Gain of phosphorylation at G152 (P = 0.0102);
MVP		0.27
ClinPred		0.71	D
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.033
gMVP		0.37

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

LitVar

Other links and lift over

dbSNP: rs758461827; hg19: chr1-231473038;