rs56309301

Variant names:

• chr2-189873586-A-C
• rs56309301
• NM_000534.5:c.2564A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-189873586-A-C
• chr2-189873586-A-G
• chr2-189873586-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000534.5(PMS1):​c.2564A>C​(p.Asn855Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PMS1 NM_000534.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11
• Publications: 5 publications found

Genes affected

PMS1 (HGNC:9121): (PMS1 homolog 1, mismatch repair system component) This gene encodes a protein belonging to the DNA mismatch repair mutL/hexB family. This protein is thought to be involved in the repair of DNA mismatches, and it can form heterodimers with MLH1, a known DNA mismatch repair protein. Mutations in this gene cause hereditary nonpolyposis colorectal cancer type 3 (HNPCC3) either alone or in combination with mutations in other genes involved in the HNPCC phenotype, which is also known as Lynch syndrome. [provided by RefSeq, Jul 2008]

PMS1 Gene-Disease associations (from GenCC):

• Lynch syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000300477 (HGNC:):

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=0.22272989).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000534.5. 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
	PMS1	NM_000534.5	MANE Select	c.2564A>C	p.Asn855Thr	missense	Exon 12 of 13	NP_000525.1
	PMS1	NM_001321045.2		c.2564A>C	p.Asn855Thr	missense	Exon 13 of 14	NP_001307974.1
	PMS1	NM_001321047.2		c.2564A>C	p.Asn855Thr	missense	Exon 12 of 13	NP_001307976.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMS1	ENST00000441310.7	TSL:1 MANE Select	c.2564A>C	p.Asn855Thr	missense	Exon 12 of 13	ENSP00000406490.3
	PMS1	ENST00000409593.5	TSL:1	c.1433A>C	p.Asn478Thr	missense	Exon 6 of 7	ENSP00000387169.1
	PMS1	ENST00000921104.1		c.2672A>C	p.Asn891Thr	missense	Exon 13 of 14	ENSP00000591163.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.031	T
Eigen	Benign	0.00042
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.22	T
MetaSVM	Uncertain	0.39	D
MutationAssessor	Benign	1.3	L
PhyloP100		2.1
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.22
Sift	Benign	0.21	T
Sift4G	Benign	0.25	T
Polyphen		0.048	B
Vest4		0.41
MutPred		0.37		Gain of ubiquitination at K851 (P = 0.1025)
MVP		0.99
MPC		0.063
ClinPred		0.52	D
GERP RS		4.8
Varity_R		0.066
gMVP		0.27
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

dbSNP: rs56309301; hg19: chr2-190738312;