1-231352778-C-A

Position:

• chr1-231352778-C-A

Variant summary

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

The NM_032018.7(SPRTN):​c.887C>A​(p.Pro296His) variant causes a missense 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P296L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPRTN NM_032018.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149

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]

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 (MetaRNN=0.06291741).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPRTN	NM_032018.7	c.887C>A	p.Pro296His	missense_variant	5/5	ENST00000295050.12	NP_114407.3
SPRTN	XM_006711818.4	c.758C>A	p.Pro253His	missense_variant	4/4		XP_006711881.1
SPRTN	NM_001010984.4	c.*1172C>A		3_prime_UTR_variant	4/4		NP_001010984.1
SPRTN	NM_001261462.3	c.*1172C>A		3_prime_UTR_variant	3/3		NP_001248391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPRTN	ENST00000295050.12	c.887C>A	p.Pro296His	missense_variant	5/5	1	NM_032018.7	ENSP00000295050	P1
SPRTN	ENST00000391858.8	c.*1172C>A		3_prime_UTR_variant	4/4	1		ENSP00000375731
SPRTN	ENST00000366644.3			downstream_gene_variant		5		ENSP00000355604
SPRTN	ENST00000469904.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 58

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.84
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.029
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.050	T
Polyphen		0.41	B
Vest4		0.15
MutPred		0.18		Gain of MoRF binding (P = 0.0533);
MVP		0.14
MPC		0.051
ClinPred		0.10	T
GERP RS		1.3
Varity_R		0.052
gMVP		0.56

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: rs2437150; hg19: chr1-231488524;