8-126556849-C-T

Position:

• chr8-126556849-C-T

Variant summary

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

The NM_174911.5(LRATD2):​c.541G>A​(p.Val181Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,453,814 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LRATD2 NM_174911.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.16

Genes affected

LRATD2 (HGNC:24166): (LRAT domain containing 2) Located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PCAT1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRATD2	NM_174911.5	c.541G>A	p.Val181Met	missense_variant	2/2	ENST00000304916.4	NP_777571.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRATD2	ENST00000304916.4	c.541G>A	p.Val181Met	missense_variant	2/2	1	NM_174911.5	ENSP00000302578.3
LRATD2	ENST00000652209.1	c.541G>A	p.Val181Met	missense_variant	1/1			ENSP00000498944.1
PCAT1	ENST00000524320.2	n.527C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453814 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723498

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 17, 2023

The c.541G>A (p.V181M) alteration is located in exon 2 (coding exon 1) of the FAM84B gene. This alteration results from a G to A substitution at nucleotide position 541, causing the valine (V) at amino acid position 181 to be replaced by a methionine (M). 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	0.79
BayesDel_addAF	Uncertain	0.084	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.35
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.9	L
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.64
MutPred		0.58		Gain of catalytic residue at V181 (P = 0.0578);
MVP		0.51
MPC		1.7
ClinPred		0.89	D
GERP RS		4.0
Varity_R		0.25
gMVP		0.83

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: chr8-127569094;