1-231347825-AT-GC

Variant names:

• chr1-231347825-AT-GC
• NM_032018.7:c.350_351delATinsGC
• SPRTN p.Tyr117Cys

Variant summary

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

The NM_032018.7(SPRTN):​c.350_351delATinsGC​(p.Tyr117Cys) variant causes a missense change. 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: 32)
• Consequence: SPRTN NM_032018.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.61
• Publications: 0 publications found

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]

SPRTN Gene-Disease associations (from GenCC):

• progeroid features-hepatocellular carcinoma predisposition syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Orphanet, Ambry Genetics

ACMG classification

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

• PS1: Transcript NM_032018.7 (SPRTN) 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_032018.7. 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
	SPRTN	NM_032018.7	MANE Select	c.350_351delATinsGC	p.Tyr117Cys	missense	N/A	NP_114407.3
	SPRTN	NM_001010984.4		c.350_351delATinsGC	p.Tyr117Cys	missense	N/A	NP_001010984.1	Q9H040-2
	SPRTN	NM_001261462.3		c.322-3479_322-3478delATinsGC		intron	N/A	NP_001248391.1	Q9H040-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRTN	ENST00000295050.12	TSL:1 MANE Select	c.350_351delATinsGC	p.Tyr117Cys	missense	N/A	ENSP00000295050.7	Q9H040-1
	SPRTN	ENST00000391858.8	TSL:1	c.350_351delATinsGC	p.Tyr117Cys	missense	N/A	ENSP00000375731.4	Q9H040-2
	SPRTN	ENST00000366644.3	TSL:5	c.38_39delATinsGC	p.Tyr13Cys	missense	N/A	ENSP00000355604.3	B1AKT1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.6

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: chr1-231483571;