chr21-41801353-C-T

Variant names:

• chr21-41801353-C-T
• rs771684064
• NM_001040424.3:c.3313G>A

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.3313G>A​(p.Ala1105Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,452,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: PRDM15 NM_001040424.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.66
• Publications: 1 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=0.17408368).

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.3313G>A	p.Ala1105Thr	missense	Exon 24 of 24	NP_001035514.2	P57071-7
	PRDM15	NM_022115.7		c.3511G>A	p.Ala1171Thr	missense	Exon 31 of 31	NP_071398.5
	PRDM15	NM_001282934.2		c.3373G>A	p.Ala1125Thr	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.3313G>A	p.Ala1105Thr	missense	Exon 24 of 24	ENSP00000381556.2	P57071-7
	PRDM15	ENST00000269844.5	TSL:1	c.3511G>A	p.Ala1171Thr	missense	Exon 31 of 31	ENSP00000269844.4	A0AB56DNF6
	PRDM15	ENST00000422911.6	TSL:1	c.3373G>A	p.Ala1125Thr	missense	Exon 25 of 25	ENSP00000408592.2	P57071-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000811 AC: 2 AN: 246684 AF XY: 0.0000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1452604 Hom.: 0 Cov.: 67 AF XY: 0.00000555 AC XY: 4 AN XY: 721032

African (AFR) AF: 0.00 AC: 0 AN: 33350

American (AMR) AF: 0.00 AC: 0 AN: 44352

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25674

East Asian (EAS) AF: 0.00 AC: 0 AN: 39544

South Asian (SAS) AF: 0.0000470 AC: 4 AN: 85124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53036

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105822

Other (OTH) AF: 0.00 AC: 0 AN: 59972

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

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	0.19
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.055
Eigen_PC	Benign	0.032
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.089	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.7
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.063
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.18	T
Polyphen		0.85	P
Vest4		0.21
MutPred		0.091		Gain of glycosylation at A1471 (P = 0.0415)
MVP		0.068
MPC		0.64
ClinPred		0.41	T
GERP RS		4.5
Varity_R		0.075
gMVP		0.38
Mutation Taster		=89/11	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: rs771684064; hg19: chr21-43221513;