chr4-112646639-C-T

Variant names:

• chr4-112646639-C-T
• NM_016648.4:c.355C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016648.4(LARP7):​c.355C>T​(p.Pro119Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000688 in 1,453,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: LARP7 NM_016648.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.57
• Publications: 0 publications found

Genes affected

LARP7 (HGNC:24912): (La ribonucleoprotein 7, transcriptional regulator) This gene encodes a protein which is found in the 7SK snRNP (small nuclear ribonucleoprotein). This snRNP complex inhibits a cyclin-dependent kinase, positive transcription elongation factor b, which is required for paused RNA polymerase II at a promoter to begin transcription elongation. A pseudogene of this gene is located on chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

MIR302CHG (HGNC:41070): (miR-302/367 cluster host gene)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3919364).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016648.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LARP7	NM_016648.4	MANE Select	c.355C>T	p.Pro119Ser	missense	Exon 4 of 13	NP_057732.2	Q4G0J3-1
	LARP7	NM_001370974.1		c.355C>T	p.Pro119Ser	missense	Exon 4 of 13	NP_001357903.1	A0A8Q3SHN7
	LARP7	NM_001370975.1		c.355C>T	p.Pro119Ser	missense	Exon 4 of 13	NP_001357904.1	A0A8Q3SHN7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LARP7	ENST00000344442.10	TSL:2 MANE Select	c.355C>T	p.Pro119Ser	missense	Exon 4 of 13	ENSP00000344950.5	Q4G0J3-1
	LARP7	ENST00000509061.5	TSL:1	c.355C>T	p.Pro119Ser	missense	Exon 6 of 15	ENSP00000422626.2	Q4G0J3-1
	LARP7	ENST00000509622.5	TSL:1	n.*114C>T		non_coding_transcript_exon	Exon 4 of 13	ENSP00000422451.1	D6RBH8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000688 AC: 10 AN: 1453516 Hom.: 0 Cov.: 30 AF XY: 0.00000692 AC XY: 5 AN XY: 722712

African (AFR) AF: 0.00 AC: 0 AN: 33342

American (AMR) AF: 0.00 AC: 0 AN: 43962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25930

East Asian (EAS) AF: 0.00 AC: 0 AN: 39472

South Asian (SAS) AF: 0.00 AC: 0 AN: 84760

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52892

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5626

European-Non Finnish (NFE) AF: 0.00000903 AC: 10 AN: 1107564

Other (OTH) AF: 0.00 AC: 0 AN: 59968

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.033	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Benign	0.000050	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.6
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.14
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.47
MutPred		0.28		Gain of phosphorylation at P119 (P = 0.0185)
MVP		0.80
MPC		0.21
ClinPred		0.98	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.53
gMVP		0.59
Mutation Taster		=32/68	disease causing

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

hg19: chr4-113567795;