1-109281155-T-C

Position:

• chr1-109281155-T-C

Variant summary

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

The NM_001032291.3(PSRC1):​c.616A>G​(p.Ser206Gly) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PSRC1 NM_001032291.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0690

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=0.063551694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSRC1	NM_001032291.3	c.616A>G	p.Ser206Gly	missense_variant	5/8	ENST00000369909.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSRC1	ENST00000369909.7	c.616A>G	p.Ser206Gly	missense_variant	5/8	1	NM_001032291.3	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 22, 2023

The c.616A>G (p.S206G) alteration is located in exon 5 (coding exon 4) of the PSRC1 gene. This alteration results from a A to G substitution at nucleotide position 616, causing the serine (S) at amino acid position 206 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.5
DANN	Benign	0.96
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.56	T;.;.;T;T;.;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.064	T;T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.46	N;N;N;N;N;N;.
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.9	N;N;N;N;.;N;N
REVEL	Benign	0.038
Sift	Benign	0.20	T;T;T;T;.;T;T
Sift4G	Benign	0.39	T;T;T;T;T;T;.
Polyphen		0.0010	B;B;B;B;B;B;.
Vest4		0.22
MutPred		0.27		Loss of glycosylation at S206 (P = 0.003);Loss of glycosylation at S206 (P = 0.003);Loss of glycosylation at S206 (P = 0.003);Loss of glycosylation at S206 (P = 0.003);Loss of glycosylation at S206 (P = 0.003);Loss of glycosylation at S206 (P = 0.003);Loss of glycosylation at S206 (P = 0.003);
MVP		0.45
MPC		0.16
ClinPred		0.065	T
GERP RS		-0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.033
gMVP		0.059

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: rs1657032167; hg19: chr1-109823777;