7-16558913-A-G

Variant names:

• chr7-16558913-A-G
• rs946278146
• NM_001195280.2:c.341A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001195280.2(LRRC72):​c.341A>G​(p.His114Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000044 in 1,362,778 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: LRRC72 NM_001195280.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.00
• Publications: 0 publications found

Genes affected

LRRC72 (HGNC:42972): (leucine rich repeat containing 72)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.113080144).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC72	NM_001195280.2	c.341A>G	p.His114Arg	missense_variant	Exon 5 of 9	ENST00000401542.3	NP_001182209.1
LRRC72	XM_011515057.2	c.341A>G	p.His114Arg	missense_variant	Exon 5 of 10		XP_011513359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC72	ENST00000401542.3	c.341A>G	p.His114Arg	missense_variant	Exon 5 of 9	5	NM_001195280.2	ENSP00000384971.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000440 AC: 6 AN: 1362778 Hom.: 0 Cov.: 29 AF XY: 0.00000298 AC XY: 2 AN XY: 671852

African (AFR) AF: 0.00 AC: 0 AN: 30632

American (AMR) AF: 0.00 AC: 0 AN: 33616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24300

East Asian (EAS) AF: 0.00 AC: 0 AN: 34372

South Asian (SAS) AF: 0.00 AC: 0 AN: 73594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46650

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5560

European-Non Finnish (NFE) AF: 0.00000567 AC: 6 AN: 1058006

Other (OTH) AF: 0.00 AC: 0 AN: 56048

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.341A>G (p.H114R) alteration is located in exon 5 (coding exon 5) of the LRRC72 gene. This alteration results from a A to G substitution at nucleotide position 341, causing the histidine (H) at amino acid position 114 to be replaced by an arginine (R). 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	Benign	0.089
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.60
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.71	N
PhyloP100		3.0
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.085
Sift	Benign	0.19	T
Sift4G	Benign	0.28	T
Vest4		0.20
MutPred		0.52		Loss of helix (P = 0.0376);
MVP		0.076
ClinPred		0.11	T
GERP RS		4.5
Varity_R		0.099
gMVP		0.095
Mutation Taster		=93/7	polymorphism

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

dbSNP: rs946278146; hg19: chr7-16598538;