16-90075069-T-G

Variant names:

• chr16-90075069-T-G
• rs7196459
• NM_001098173.2:c.194-46A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098173.2(PRDM7):​c.194-46A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.95 in 152,140 control chromosomes in the GnomAD database, including 68,784 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.95 (68784 hom., cov: 29)
  • Exomes 𝑓: 0.93 (627710 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRDM7 NM_001098173.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.977
• Publications: 18 publications found

Genes affected

PRDM7 (HGNC:9351): (PR/SET domain 7) This gene encodes a member of a family of proteins that may have roles in transcription and other nuclear processes. The encoded protein contains a KRAB (Kruppel-associated box) domain -A box and a SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain and may function as a histone methyltransferase. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM7	NM_001098173.2	c.194-46A>C		intron_variant	Intron 3 of 10	ENST00000449207.8	NP_001091643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM7	ENST00000449207.8	c.194-46A>C		intron_variant	Intron 3 of 10	1	NM_001098173.2	ENSP00000396732.2
PRDM7	ENST00000564210.2	n.70-46A>C		intron_variant	Intron 1 of 5	5		ENSP00000457667.1
PRDM7	ENST00000568473.5	n.194-46A>C		intron_variant	Intron 2 of 5	5		ENSP00000455390.1
PRDM7	ENST00000569206.1	n.675-46A>C		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.950 AC: 144473 AN: 152022 Hom.: 68725 Cov.: 29

Gnomad AFR AF: 0.987

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.975

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.989

Gnomad FIN AF: 0.935

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.955

GnomAD2 exomes AF: 0.946 AC: 234764 AN: 248184 AF XY: 0.947

Gnomad AFR exome AF: 0.989

Gnomad AMR exome AF: 0.979

Gnomad ASJ exome AF: 0.907

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.931

Gnomad NFE exome AF: 0.917

Gnomad OTH exome AF: 0.943

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.929 AC: 1349761 AN: 1452528 Hom.: 627710 Cov.: 29 AF XY: 0.931 AC XY: 673137 AN XY: 723170

African (AFR) AF: 0.990 AC: 32963 AN: 33288

American (AMR) AF: 0.979 AC: 43696 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 23662 AN: 26070

East Asian (EAS) AF: 1.00 AC: 39646 AN: 39646

South Asian (SAS) AF: 0.985 AC: 84718 AN: 86034

European-Finnish (FIN) AF: 0.932 AC: 49731 AN: 53362

Middle Eastern (MID) AF: 0.977 AC: 5617 AN: 5750

European-Non Finnish (NFE) AF: 0.918 AC: 1013352 AN: 1103644

Other (OTH) AF: 0.938 AC: 56376 AN: 60086

GnomAD4 genome AF: 0.950 AC: 144591 AN: 152140 Hom.: 68784 Cov.: 29 AF XY: 0.953 AC XY: 70844 AN XY: 74368

African (AFR) AF: 0.987 AC: 40951 AN: 41502

American (AMR) AF: 0.975 AC: 14919 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.909 AC: 3156 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5160 AN: 5162

South Asian (SAS) AF: 0.989 AC: 4761 AN: 4816

European-Finnish (FIN) AF: 0.935 AC: 9898 AN: 10584

Middle Eastern (MID) AF: 0.983 AC: 287 AN: 292

European-Non Finnish (NFE) AF: 0.921 AC: 62632 AN: 67994

Other (OTH) AF: 0.955 AC: 2017 AN: 2112

Alfa AF: 0.933 Hom.: 103001

Bravo AF: 0.954

Asia WGS AF: 0.989 AC: 3440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.72
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism (auto)

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: rs7196459; hg19: chr16-90141477;