chr21-41801469-T-A

Variant names:

• chr21-41801469-T-A
• NM_001040424.3:c.3197A>T

Variant summary

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

The NM_001040424.3(PRDM15):​c.3197A>T​(p.Gln1066Leu) 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. 16/22 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: PRDM15 NM_001040424.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.09
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12915784).

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.3197A>T	p.Gln1066Leu	missense	Exon 24 of 24	NP_001035514.2	P57071-7
	PRDM15	NM_022115.7		c.3395A>T	p.Gln1132Leu	missense	Exon 31 of 31	NP_071398.5
	PRDM15	NM_001282934.2		c.3257A>T	p.Gln1086Leu	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.3197A>T	p.Gln1066Leu	missense	Exon 24 of 24	ENSP00000381556.2	P57071-7
	PRDM15	ENST00000269844.5	TSL:1	c.3395A>T	p.Gln1132Leu	missense	Exon 31 of 31	ENSP00000269844.4	A0AB56DNF6
	PRDM15	ENST00000422911.6	TSL:1	c.3257A>T	p.Gln1086Leu	missense	Exon 25 of 25	ENSP00000408592.2	P57071-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 67

GnomAD4 genome Cov.: 32

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	Benign	0.11
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.1
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.15
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.021	D
Polyphen		0.96	P
Vest4		0.24
MutPred		0.26		Gain of catalytic residue at Q1432 (P = 0.0041)
MVP		0.068
MPC		0.54
ClinPred		0.51	D
GERP RS		1.9
Varity_R		0.078
gMVP		0.53
Mutation Taster		=81/19	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: chr21-43221629;