NM_016648.4:c.23A>G

Variant names:

• chr4-112644692-A-G
• rs758503259
• NM_016648.4:c.23A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016648.4(LARP7):​c.23A>G​(p.Gln8Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,605,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: LARP7 NM_016648.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.164
• Publications: 3 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]

LARP7 Gene-Disease associations (from GenCC):

• microcephalic primordial dwarfism, Alazami type

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.026677608).

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.23A>G	p.Gln8Arg	missense	Exon 2 of 13	NP_057732.2	Q4G0J3-1
	LARP7	NM_001370974.1		c.23A>G	p.Gln8Arg	missense	Exon 2 of 13	NP_001357903.1	A0A8Q3SHN7
	LARP7	NM_001370975.1		c.23A>G	p.Gln8Arg	missense	Exon 2 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.23A>G	p.Gln8Arg	missense	Exon 2 of 13	ENSP00000344950.5	Q4G0J3-1
	LARP7	ENST00000509061.5	TSL:1	c.23A>G	p.Gln8Arg	missense	Exon 4 of 15	ENSP00000422626.2	Q4G0J3-1
	LARP7	ENST00000509622.5	TSL:1	n.23A>G		non_coding_transcript_exon	Exon 2 of 13	ENSP00000422451.1	D6RBH8

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151992 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000368 AC: 9 AN: 244844 AF XY: 0.0000603

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000299

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000206 AC: 30 AN: 1453622 Hom.: 0 Cov.: 30 AF XY: 0.0000318 AC XY: 23 AN XY: 723128

African (AFR) AF: 0.0000909 AC: 3 AN: 32994

American (AMR) AF: 0.00 AC: 0 AN: 43806

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25892

East Asian (EAS) AF: 0.00 AC: 0 AN: 39468

South Asian (SAS) AF: 0.000272 AC: 23 AN: 84606

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107958

Other (OTH) AF: 0.0000667 AC: 4 AN: 59938

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151992 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74242

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10482

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000580 AC: 7

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	Benign	0.063
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	2.8
DANN	Benign	0.94
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.29	N
PhyloP100		0.16
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.045
Sift	Benign	0.58	T
Sift4G	Benign	0.59	T
Polyphen		0.15	B
Vest4		0.20
MutPred		0.11		Loss of glycosylation at K10 (P = 0.2091)
MVP		0.32
MPC		0.054
ClinPred		0.023	T
GERP RS		-0.52
PromoterAI		-0.0090	Neutral
Varity_R		0.022
gMVP		0.052
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs758503259; hg19: chr4-113565848;