1-109281176-C-A

Variant names:

• chr1-109281176-C-A
• rs199962633
• NM_001032291.3:c.595G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001032291.3(PSRC1):​c.595G>T​(p.Val199Phe) 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. 15/22 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. V199L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PSRC1 NM_001032291.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06127286).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001032291.3. 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
	PSRC1	NM_001032291.3	MANE Select	c.595G>T	p.Val199Phe	missense	Exon 5 of 8	NP_001027462.1	Q6PGN9-2
	PSRC1	NM_001363309.2		c.595G>T	p.Val199Phe	missense	Exon 5 of 7	NP_001350238.1	Q6PGN9-1
	PSRC1	NM_001394005.1		c.595G>T	p.Val199Phe	missense	Exon 5 of 7	NP_001380934.1	Q6PGN9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSRC1	ENST00000369909.7	TSL:1 MANE Select	c.595G>T	p.Val199Phe	missense	Exon 5 of 8	ENSP00000358925.2	Q6PGN9-2
	PSRC1	ENST00000369907.7	TSL:1	c.595G>T	p.Val199Phe	missense	Exon 5 of 8	ENSP00000358923.3	Q6PGN9-2
	PSRC1	ENST00000369904.7	TSL:1	c.595G>T	p.Val199Phe	missense	Exon 5 of 8	ENSP00000358920.3	Q6PGN9-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.039
DANN	Benign	0.82
DEOGEN2	Benign	0.058	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		-1.1
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.036
Sift	Benign	0.098	T
Sift4G	Uncertain	0.044	D
Polyphen		0.0	B
Vest4		0.30
MutPred		0.23		Gain of catalytic residue at V199 (P = 0.0874)
MVP		0.26
MPC		0.26
ClinPred		0.074	T
GERP RS		-6.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.038
gMVP		0.088
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs199962633; hg19: chr1-109823798;