4-75013066-G-C

Variant names:

• chr4-75013066-G-C
• rs750906461
• NM_015393.4:c.685G>C

Variant summary

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

The NM_015393.4(PARM1):​c.685G>C​(p.Val229Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,708 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: PARM1 NM_015393.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.584

Genes affected

PARM1 (HGNC:24536): (prostate androgen-regulated mucin-like protein 1) Predicted to be involved in positive regulation of telomerase activity. Located in several cellular components, including Golgi apparatus; endosome; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000248165 (HGNC:):

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=0.07983282).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARM1	NM_015393.4	c.685G>C	p.Val229Leu	missense_variant	Exon 2 of 4	ENST00000307428.7	NP_056208.2
PARM1	XM_011531833.1	c.790G>C	p.Val264Leu	missense_variant	Exon 3 of 5		XP_011530135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARM1	ENST00000307428.7	c.685G>C	p.Val229Leu	missense_variant	Exon 2 of 4	1	NM_015393.4	ENSP00000370224.3
PARM1	ENST00000513238.5	c.44-20817G>C		intron_variant	Intron 1 of 2	3		ENSP00000424276.1
ENSG00000248165	ENST00000513770.1	n.52-13895C>G		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249184 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135176

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 SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461708 Hom.: 0 Cov.: 41 AF XY: 0.00000275 AC XY: 2 AN XY: 727138

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.059
Sift	Benign	0.053	T
Sift4G	Benign	0.34	T
Polyphen		0.36	B
Vest4		0.12
MutPred		0.27		Loss of catalytic residue at M230 (P = 0.0683);
MVP		0.22
MPC		0.13
ClinPred		0.15	T
GERP RS		4.2
Varity_R		0.038
gMVP		0.25

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: rs750906461; hg19: chr4-75938276;