chr11-61416447-A-T

Variant names:

• chr11-61416447-A-T
• NM_001142565.3:c.596T>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001142565.3(CPSF7):​c.596T>A​(p.Leu199His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: CPSF7 NM_001142565.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18631503).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPSF7	NM_001142565.3	c.596T>A	p.Leu199His	missense_variant	Exon 6 of 10	ENST00000439958.8	NP_001136037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPSF7	ENST00000439958.8	c.596T>A	p.Leu199His	missense_variant	Exon 6 of 10	1	NM_001142565.3	ENSP00000397203.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.027	.;T;.;.;T;.;T;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	T;T;.;T;T;T;T;T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.19	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	.;N;.;.;.;.;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	0.38	N;N;N;N;N;N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.014	D;T;D;D;D;D;D;D
Sift4G	Benign	0.54	T;T;T;T;.;T;.;.
Polyphen		0.98	D;P;D;D;.;.;.;.
Vest4		0.55
MutPred		0.26		.;Loss of stability (P = 0.0103);.;.;.;.;.;.;
MVP		0.55
MPC		1.9
ClinPred		0.45	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-61183919;