chr21-41801420-C-T

Variant names:

• chr21-41801420-C-T
• rs116436673
• NM_001040424.3:c.3246G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001040424.3(PRDM15):​c.3246G>A​(p.Thr1082Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000309 in 1,613,994 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (2 hom.)
• Consequence: PRDM15 NM_001040424.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.77
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 21-41801420-C-T is Benign according to our data. Variant chr21-41801420-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2652685.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.78 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.3246G>A	p.Thr1082Thr	synonymous	Exon 24 of 24	NP_001035514.2	P57071-7
	PRDM15	NM_022115.7		c.3444G>A	p.Thr1148Thr	synonymous	Exon 31 of 31	NP_071398.5
	PRDM15	NM_001282934.2		c.3306G>A	p.Thr1102Thr	synonymous	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.3246G>A	p.Thr1082Thr	synonymous	Exon 24 of 24	ENSP00000381556.2	P57071-7
	PRDM15	ENST00000269844.5	TSL:1	c.3444G>A	p.Thr1148Thr	synonymous	Exon 31 of 31	ENSP00000269844.4	A0AB56DNF6
	PRDM15	ENST00000422911.6	TSL:1	c.3306G>A	p.Thr1102Thr	synonymous	Exon 25 of 25	ENSP00000408592.2	P57071-2

Frequencies

GnomAD3 genomes AF: 0.00173 AC: 263 AN: 152084 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000446 AC: 112 AN: 251354 AF XY: 0.000361

Gnomad AFR exome AF: 0.00535

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000160 AC: 234 AN: 1461792 Hom.: 2 Cov.: 67 AF XY: 0.000153 AC XY: 111 AN XY: 727200

African (AFR) AF: 0.00508 AC: 170 AN: 33474

American (AMR) AF: 0.000447 AC: 20 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111958

Other (OTH) AF: 0.000331 AC: 20 AN: 60384

GnomAD4 genome AF: 0.00173 AC: 264 AN: 152202 Hom.: 0 Cov.: 32 AF XY: 0.00153 AC XY: 114 AN XY: 74408

African (AFR) AF: 0.00605 AC: 251 AN: 41504

American (AMR) AF: 0.000523 AC: 8 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68006

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000737 Hom.: 0

Bravo AF: 0.00169

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	11
DANN	Benign	0.60
PhyloP100		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs116436673; hg19: chr21-43221580; COSMIC: COSV99521027; COSMIC: COSV99521027;