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:

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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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014188.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSU72	NM_014188.3	MANE Select	c.224+2952T>G		intron	N/A	NP_054907.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SSU72	ENST00000291386.4	TSL:1 MANE Select	c.224+2952T>G	intron	N/A	ENSP00000291386.3
SSU72	ENST00000359060.5	TSL:2	c.*2714T>G	3_prime_UTR	Exon 2 of 2	ENSP00000351955.3
SSU72	ENST00000378725.3	TSL:2	n.254+2952T>G	intron	N/A

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over