chr4-75012653-C-G

Variant names:

• chr4-75012653-C-G
• rs1722895199
• NM_015393.4:c.272C>G

Variant summary

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

The NM_015393.4(PARM1):​c.272C>G​(p.Thr91Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: PARM1 NM_015393.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.04

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=0.20668823).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARM1	NM_015393.4	c.272C>G	p.Thr91Ser	missense_variant	Exon 2 of 4	ENST00000307428.7	NP_056208.2
PARM1	XM_011531833.1	c.377C>G	p.Thr126Ser	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.272C>G	p.Thr91Ser	missense_variant	Exon 2 of 4	1	NM_015393.4	ENSP00000370224.3
PARM1	ENST00000513238.5	c.44-21230C>G		intron_variant	Intron 1 of 2	3		ENSP00000424276.1
ENSG00000248165	ENST00000513770.1	n.52-13482G>C		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 14, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.272C>G (p.T91S) alteration is located in exon 2 (coding exon 2) of the PARM1 gene. This alteration results from a C to G substitution at nucleotide position 272, causing the threonine (T) at amino acid position 91 to be replaced by a serine (S). 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	0.096
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	3.5
DANN	Benign	0.91
DEOGEN2	Benign	0.0052	T
Eigen	Benign	0.058
Eigen_PC	Benign	-0.014
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.30	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.21	T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.26
Sift	Benign	0.12	T
Sift4G	Benign	0.25	T
Polyphen		1.0	D
Vest4		0.095
MutPred		0.14		Gain of glycosylation at T91 (P = 0.0323);
MVP		0.79
MPC		0.17
ClinPred		0.42	T
GERP RS		5.2
Varity_R		0.053
gMVP		0.14

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: rs1722895199; hg19: chr4-75937863;