Genetic Variant SSU72:c.224+2952T>G (chr1-1561821-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014188.3(SSU72):c.224+2952T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 152,022 control chromosomes in the GnomAD database, including 23,412 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 0.50 ( 23407 hom., cov: 31)

Exomes 𝑓: 0.28 ( 5 hom. )

Consequence

SSU72
NM_014188.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0600

Publications

5 publications found

Variant links:

Genes affected

SSU72 (HGNC:25016): (SSU72 homolog, RNA polymerase II CTD phosphatase) Enables RNA polymerase II CTD heptapeptide repeat phosphatase activity. Involved in dephosphorylation of RNA polymerase II C-terminal domain and mRNA polyadenylation. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SSU72 links:

ENSG00000299413 (HGNC:):

ENSG00000299413 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSU72	NM_014188.3 link	c.224+2952T>G		intron_variant	Intron 2 of 4	ENST00000291386.4	NP_054907.1	Q9NP77-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SSU72	ENST00000291386.4 link	c.224+2952T>G	intron_variant	Intron 2 of 4	1	NM_014188.3	ENSP00000291386.3	Q9NP77-1
SSU72	ENST00000359060.5 link	c.*2714T>G	3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000351955.3	Q9NP77-2
SSU72	ENST00000378725.3 link	n.254+2952T>G	intron_variant	Intron 2 of 2	2
ENSG00000299413	ENST00000763257.1 link	n.246+22012A>C	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.495

AC:

75156

AN:

151816

Hom.:

23331

Cov.:

show subpopulations

Gnomad AFR

AF:

0.835

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.533

Gnomad ASJ

AF:

0.311

Gnomad EAS

AF:

0.864

Gnomad SAS

AF:

0.682

Gnomad FIN

AF:

0.326

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.280

Gnomad OTH

AF:

0.462

GnomAD4 exome

AF:

0.278

AC:

AN:

Hom.:

Cov.:

AF XY:

0.242

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.194

AC:

AN:

Other (OTH)

AF:

0.125

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.496

AC:

75298

AN:

151932

Hom.:

23407

Cov.:

AF XY:

0.504

AC XY:

37443

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.835

AC:

34592

AN:

41436

American (AMR)

AF:

0.533

AC:

8143

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.311

AC:

1080

AN:

3472

East Asian (EAS)

AF:

0.865

AC:

4456

AN:

5152

South Asian (SAS)

AF:

0.684

AC:

3283

AN:

4802

European-Finnish (FIN)

AF:

0.326

AC:

3447

AN:

10570

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.280

AC:

18999

AN:

67920

Other (OTH)

AF:

0.469

AC:

989

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1485

2971

4456

5942

7427

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

614

1228

1842

2456

3070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.251

Hom.:

892

Bravo

AF:

0.520

Asia WGS

AF:

0.796

AC:

2765

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

4.5

(source)

DANN

Benign

0.44

PhyloP100

-0.060

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over