chr1-109280783-G-A

Variant names:

• chr1-109280783-G-A
• rs779333680
• NM_001032291.3:c.898C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001032291.3(PSRC1):​c.898C>T​(p.His300Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000957 in 1,566,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: PSRC1 NM_001032291.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.367
• 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07633507).

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.898C>T	p.His300Tyr	missense	Exon 6 of 8	NP_001027462.1	Q6PGN9-2
	PSRC1	NM_001363309.2		c.988C>T	p.His330Tyr	missense	Exon 5 of 7	NP_001350238.1	Q6PGN9-1
	PSRC1	NM_001394005.1		c.988C>T	p.His330Tyr	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.898C>T	p.His300Tyr	missense	Exon 6 of 8	ENSP00000358925.2	Q6PGN9-2
	PSRC1	ENST00000369907.7	TSL:1	c.898C>T	p.His300Tyr	missense	Exon 6 of 8	ENSP00000358923.3	Q6PGN9-2
	PSRC1	ENST00000369904.7	TSL:1	c.797C>T	p.Thr266Ile	missense	Exon 6 of 8	ENSP00000358920.3	Q6PGN9-3

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152160 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000580 AC: 13 AN: 224182 AF XY: 0.0000584

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000128

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000102 AC: 144 AN: 1414716 Hom.: 0 Cov.: 31 AF XY: 0.0000861 AC XY: 60 AN XY: 696492

African (AFR) AF: 0.00 AC: 0 AN: 32514

American (AMR) AF: 0.00 AC: 0 AN: 41238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23324

East Asian (EAS) AF: 0.00 AC: 0 AN: 39056

South Asian (SAS) AF: 0.00 AC: 0 AN: 80412

European-Finnish (FIN) AF: 0.0000193 AC: 1 AN: 51848

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5358

European-Non Finnish (NFE) AF: 0.000130 AC: 141 AN: 1082694

Other (OTH) AF: 0.0000343 AC: 2 AN: 58272

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152160 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74332

African (AFR) AF: 0.00 AC: 0 AN: 41414

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000904 Hom.: 0

Bravo AF: 0.0000378

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000907 AC: 11

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	0.10
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.2
DANN	Benign	0.91
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.37
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.067
Sift	Benign	0.071	T
Sift4G	Benign	0.88	T
Polyphen		0.0010	B
Vest4		0.22
MutPred		0.38		Gain of phosphorylation at H330 (P = 0.0099)
MVP		0.53
MPC		0.25
ClinPred		0.11	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.060
gMVP		0.11
Mutation Taster		=98/2	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: rs779333680; hg19: chr1-109823405;