NM_001032291.3:c.*266A>C

Variant names:

• chr1-109279887-T-G
• rs14000
• NM_001032291.3:c.*266A>C

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.*266A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000257 in 389,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: PSRC1 NM_001032291.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• 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 (BayesDel_noAF=-0.8).

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.*266A>C		3_prime_UTR	Exon 8 of 8	NP_001027462.1	Q6PGN9-2
	PSRC1	NM_001363309.2		c.*266A>C		3_prime_UTR	Exon 7 of 7	NP_001350238.1	Q6PGN9-1
	PSRC1	NM_001394005.1		c.*266A>C		3_prime_UTR	Exon 7 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.*266A>C		3_prime_UTR	Exon 8 of 8	ENSP00000358925.2	Q6PGN9-2
	PSRC1	ENST00000369907.7	TSL:1	c.*266A>C		3_prime_UTR	Exon 8 of 8	ENSP00000358923.3	Q6PGN9-2
	PSRC1	ENST00000369904.7	TSL:1	c.*234A>C		3_prime_UTR	Exon 8 of 8	ENSP00000358920.3	Q6PGN9-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000257 AC: 1 AN: 389268 Hom.: 0 Cov.: 3 AF XY: 0.00000492 AC XY: 1 AN XY: 203334

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 11828

American (AMR) AF: 0.00 AC: 0 AN: 17466

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11924

East Asian (EAS) AF: 0.00 AC: 0 AN: 29876

South Asian (SAS) AF: 0.00 AC: 0 AN: 32540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28826

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1706

European-Non Finnish (NFE) AF: 0.00000431 AC: 1 AN: 232106

Other (OTH) AF: 0.00 AC: 0 AN: 22996

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.8
DANN	Benign	0.71
PhyloP100		0.0010
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

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: rs14000; hg19: chr1-109822509;