1-109280796-C-A

Variant names:

• chr1-109280796-C-A
• ENST00000369904.7:c.784G>T

Variant summary

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

The NM_001005290.4(PSRC1):​c.784G>T​(p.Ala262Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,430,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/14 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. A262T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PSRC1 NM_001005290.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279

Genes affected

PSRC1 (HGNC:24472): (proline and serine rich coiled-coil 1) This gene encodes a proline-rich protein that is a target for regulation by the tumor suppressor protein p53. The encoded protein plays an important role in mitosis by recruiting and regulating microtubule depolymerases that destabalize microtubules. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Apr 2014]

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=0.03787464).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSRC1	NM_001032291.3	c.885G>T	p.Val295Val	synonymous_variant	Exon 6 of 8	ENST00000369909.7	NP_001027462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSRC1	ENST00000369909.7	c.885G>T	p.Val295Val	synonymous_variant	Exon 6 of 8	1	NM_001032291.3	ENSP00000358925.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1430728 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 706842

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: 0.0000121

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	0.28
DANN	Benign	0.88
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.072
Sift	Benign	0.44	T
Sift4G	Benign	0.40	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.22		Gain of relative solvent accessibility (P = 0.0023);
MVP		0.26
ClinPred		0.028	T
GERP RS		-1.7

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: chr1-109823418;