4-112646639-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LARP7	NM_016648.4	c.355C>T	p.Pro119Ser	missense_variant	Exon 4 of 13	ENST00000344442.10	NP_057732.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LARP7	ENST00000344442.10	c.355C>T	p.Pro119Ser	missense_variant	Exon 4 of 13	2	NM_016648.4	ENSP00000344950.5

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000903

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Jan 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.355C>T (p.P119S) alteration is located in exon 4 (coding exon 3) of the LARP7 gene. This alteration results from a C to T substitution at nucleotide position 355, causing the proline (P) at amino acid position 119 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;.;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Benign	0.000050	N
LIST_S2	Uncertain	0.93	.;D;D;D;D;D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.33	T;T;T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.1	M;.;.;.;M;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.5	D;D;D;D;D;D
REVEL	Benign	0.14
Sift	Uncertain	0.0060	D;D;D;D;D;D
Sift4G	Uncertain	0.014	D;D;D;T;D;D
Polyphen		1.0	D;.;.;P;D;.
Vest4		0.47
MutPred		0.28		Gain of phosphorylation at P119 (P = 0.0185);.;Gain of phosphorylation at P119 (P = 0.0185);Gain of phosphorylation at P119 (P = 0.0185);Gain of phosphorylation at P119 (P = 0.0185);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-113567795;