NM_001040424.3:c.3421T>A

Variant names:

• chr21-41801245-A-T
• NM_001040424.3:c.3421T>A

Variant summary

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

The NM_001040424.3(PRDM15):​c.3421T>A​(p.Tyr1141Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRDM15 NM_001040424.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.98
• Publications: 0 publications found

Genes affected

PRDM15 (HGNC:13999): (PR/SET domain 15) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and promoter-specific chromatin binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II; regulation of signal transduction; and regulation of stem cell division. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040424.3. 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
	PRDM15	NM_001040424.3	MANE Select	c.3421T>A	p.Tyr1141Asn	missense	Exon 24 of 24	NP_001035514.2	P57071-7
	PRDM15	NM_022115.7		c.3619T>A	p.Tyr1207Asn	missense	Exon 31 of 31	NP_071398.5
	PRDM15	NM_001282934.2		c.3481T>A	p.Tyr1161Asn	missense	Exon 25 of 25	NP_001269863.2	P57071-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM15	ENST00000398548.6	TSL:1 MANE Select	c.3421T>A	p.Tyr1141Asn	missense	Exon 24 of 24	ENSP00000381556.2	P57071-7
	PRDM15	ENST00000269844.5	TSL:1	c.3619T>A	p.Tyr1207Asn	missense	Exon 31 of 31	ENSP00000269844.4	A0AB56DNF6
	PRDM15	ENST00000422911.6	TSL:1	c.3481T>A	p.Tyr1161Asn	missense	Exon 25 of 25	ENSP00000408592.2	P57071-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

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	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.031	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.84	T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		8.0
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.69
MutPred		0.29		Loss of phosphorylation at Y1507 (P = 0.0525)
MVP		0.20
MPC		1.1
ClinPred		0.85	D
GERP RS		4.6
Varity_R		0.36
gMVP		0.70
Mutation Taster		=65/35	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

hg19: chr21-43221405;