NM_001032291.3:c.395A>C

Variant names:

• chr1-109281743-T-G
• NM_001032291.3:c.395A>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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
• 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: Uncertain_significance. The variant received 0 ACMG points.

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

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.395A>C	p.Asn132Thr	missense	Exon 4 of 8	NP_001027462.1	Q6PGN9-2
	PSRC1	NM_001363309.2		c.395A>C	p.Asn132Thr	missense	Exon 4 of 7	NP_001350238.1	Q6PGN9-1
	PSRC1	NM_001394005.1		c.395A>C	p.Asn132Thr	missense	Exon 4 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.395A>C	p.Asn132Thr	missense	Exon 4 of 8	ENSP00000358925.2	Q6PGN9-2
	PSRC1	ENST00000369907.7	TSL:1	c.395A>C	p.Asn132Thr	missense	Exon 4 of 8	ENSP00000358923.3	Q6PGN9-2
	PSRC1	ENST00000369904.7	TSL:1	c.395A>C	p.Asn132Thr	missense	Exon 4 of 8	ENSP00000358920.3	Q6PGN9-3

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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.056	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.78
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.039
Sift	Benign	0.041	D
Sift4G	Uncertain	0.038	D
Polyphen		0.034	B
Vest4		0.17
MutPred		0.089		Gain of glycosylation at N132 (P = 0.0436)
MVP		0.45
MPC		0.21
ClinPred		0.26	T
GERP RS		3.7
PromoterAI		0.051	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.088
gMVP		0.083
Mutation Taster		=88/12	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

hg19: chr1-109824365;