rs1026159326

Variant names:

• chr11-61421442-T-A
• rs1026159326
• NM_001142565.3:c.221A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-61421442-T-A
• chr11-61421442-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001142565.3(CPSF7):​c.221A>T​(p.Tyr74Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPSF7 NM_001142565.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.24

Genes affected

CPSF7 (HGNC:30098): (cleavage and polyadenylation specific factor 7) Cleavage factor Im (CFIm) is one of six factors necessary for correct cleavage and polyadenylation of pre-mRNAs. CFIm is composed of three different subunits of 25, 59, and 68 kDa, and it functions as a heterotetramer, with a dimer of the 25 kDa subunit binding to two of the 59 or 68 kDa subunits. The protein encoded by this gene represents the 59 kDa subunit, which can interact with the splicing factor U2 snRNP Auxiliary Factor (U2AF) 65 to link the splicing and polyadenylation complexes. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPSF7	NM_001142565.3	c.221A>T	p.Tyr74Phe	missense_variant	Exon 3 of 10	ENST00000439958.8	NP_001136037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPSF7	ENST00000439958.8	c.221A>T	p.Tyr74Phe	missense_variant	Exon 3 of 10	1	NM_001142565.3	ENSP00000397203.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.082	.;T;.;.;T;.;T;T;T;.;.;T;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D;.;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.0046	T
MetaRNN	Uncertain	0.43	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.0	.;M;M;M;.;.;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.9	N;N;N;N;N;N;N;N;D;N;N;N;.
REVEL	Benign	0.20
Sift	Benign	0.041	D;T;T;T;D;T;D;D;D;D;D;D;.
Sift4G	Benign	0.39	T;T;T;T;.;T;.;.;D;.;.;.;D
Polyphen		0.99	D;P;D;D;.;.;.;.;D;.;.;.;.
Vest4		0.48
MutPred		0.45		.;Loss of catalytic residue at Y74 (P = 0.0063);Loss of catalytic residue at Y74 (P = 0.0063);Loss of catalytic residue at Y74 (P = 0.0063);Loss of catalytic residue at Y74 (P = 0.0063);Loss of catalytic residue at Y74 (P = 0.0063);Loss of catalytic residue at Y74 (P = 0.0063);Loss of catalytic residue at Y74 (P = 0.0063);Loss of catalytic residue at Y74 (P = 0.0063);Loss of catalytic residue at Y74 (P = 0.0063);Loss of catalytic residue at Y74 (P = 0.0063);Loss of catalytic residue at Y74 (P = 0.0063);Loss of catalytic residue at Y74 (P = 0.0063);
MVP		0.54
MPC		1.7
ClinPred		0.66	D
GERP RS		5.7
Varity_R		0.19
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1026159326; hg19: chr11-61188914;