21-41801469-T-A

Position:

• chr21-41801469-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 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. 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: PRDM15 NM_001040424.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.09

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]

PRDM15 (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=0.12915784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM15	NM_001040424.3	c.3197A>T	p.Gln1066Leu	missense_variant	24/24	ENST00000398548.6	NP_001035514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM15	ENST00000398548.6	c.3197A>T	p.Gln1066Leu	missense_variant	24/24	1	NM_001040424.3	ENSP00000381556.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 67

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.4295A>T (p.Q1432L) alteration is located in exon 31 (coding exon 31) of the PRDM15 gene. This alteration results from a A to T substitution at nucleotide position 4295, causing the glutamine (Q) at amino acid position 1432 to be replaced by a leucine (L). 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	0.11
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.025	.;.;T;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.83	T;T;T;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	.;.;.;L
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.70	N;N;N;N
REVEL	Benign	0.15
Sift	Uncertain	0.0080	D;D;D;D
Sift4G	Uncertain	0.021	D;D;D;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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-43221629;