1-109281743-T-G

Position:

• chr1-109281743-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001032291.3(PSRC1):​c.395A>C​(p.Asn132Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PSRC1 NM_001032291.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.782

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0925377).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSRC1	NM_001032291.3	c.395A>C	p.Asn132Thr	missense_variant	4/8	ENST00000369909.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSRC1	ENST00000369909.7	c.395A>C	p.Asn132Thr	missense_variant	4/8	1	NM_001032291.3	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461876 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

May 11, 2022

The c.395A>C (p.N132T) alteration is located in exon 4 (coding exon 3) of the PSRC1 gene. This alteration results from a A to C substitution at nucleotide position 395, causing the asparagine (N) at amino acid position 132 to be replaced by a threonine (T). 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	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.056	.;.;.;.;T;.;T;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.78	T;.;.;T;T;.;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.093	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N;N;N;N;N;N;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.3	N;N;N;N;.;N;N;N
REVEL	Benign	0.039
Sift	Benign	0.041	D;D;D;D;.;D;D;D
Sift4G	Uncertain	0.038	D;D;D;D;T;D;.;.
Polyphen		0.034	B;B;B;B;B;B;.;.
Vest4		0.17
MutPred		0.089		Gain of glycosylation at N132 (P = 0.0436);Gain of glycosylation at N132 (P = 0.0436);Gain of glycosylation at N132 (P = 0.0436);Gain of glycosylation at N132 (P = 0.0436);Gain of glycosylation at N132 (P = 0.0436);Gain of glycosylation at N132 (P = 0.0436);Gain of glycosylation at N132 (P = 0.0436);Gain of glycosylation at N132 (P = 0.0436);
MVP		0.45
MPC		0.21
ClinPred		0.26	T
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.088
gMVP		0.083

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: chr1-109824365;