rs374699943

Variant names:

• chr8-126556546-C-A
• rs374699943
• NM_174911.5:c.844G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-126556546-C-A
• chr8-126556546-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_174911.5(LRATD2):​c.844G>T​(p.Asp282Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000028 in 1,604,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: LRATD2 NM_174911.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.98
• Publications: 1 publications found

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:43022): (prostate cancer associated transcript 1) This gene produces a long non-coding RNA that promotes cell proliferation and is upregulated in prostate, colorectal, and other cancers. This RNA negatively regulates the BRCA2 tumor suppressor protein and positively regulates Myc oncoprotein. It contains binding sites for microRNAs, and may act as a sponge for microRNAs that regulate cell growth pathways. [provided by RefSeq, Dec 2017]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10052955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRATD2	NM_174911.5	c.844G>T	p.Asp282Tyr	missense_variant	Exon 2 of 2	ENST00000304916.4	NP_777571.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRATD2	ENST00000304916.4	c.844G>T	p.Asp282Tyr	missense_variant	Exon 2 of 2	1	NM_174911.5	ENSP00000302578.3
LRATD2	ENST00000652209.1	c.844G>T	p.Asp282Tyr	missense_variant	Exon 1 of 1			ENSP00000498944.1
PCAT1	ENST00000524320.2	n.224C>A		non_coding_transcript_exon_variant	Exon 1 of 2	2
LRATD2	ENST00000517458.1	n.-127G>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152274 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000506

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000265 AC: 6 AN: 226240 AF XY: 0.0000321

Gnomad AFR exome AF: 0.000229

Gnomad AMR exome AF: 0.0000619

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: 0.000180

GnomAD4 exome AF: 0.0000124 AC: 18 AN: 1451946 Hom.: 0 Cov.: 31 AF XY: 0.0000125 AC XY: 9 AN XY: 721574

African (AFR) AF: 0.000271 AC: 9 AN: 33164

American (AMR) AF: 0.0000928 AC: 4 AN: 43126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25818

East Asian (EAS) AF: 0.00 AC: 0 AN: 39352

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51642

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108276

Other (OTH) AF: 0.0000667 AC: 4 AN: 59926

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152392 Hom.: 0 Cov.: 33 AF XY: 0.000174 AC XY: 13 AN XY: 74524

African (AFR) AF: 0.000529 AC: 22 AN: 41602

American (AMR) AF: 0.000196 AC: 3 AN: 15312

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.000147

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000249 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.844G>T (p.D282Y) alteration is located in exon 2 (coding exon 1) of the FAM84B gene. This alteration results from a G to T substitution at nucleotide position 844, causing the aspartic acid (D) at amino acid position 282 to be replaced by a tyrosine (Y). 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	0.11
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.0
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.17
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.081	T
Polyphen		0.64	P
Vest4		0.33
MVP		0.68
MPC		1.2
ClinPred		0.062	T
GERP RS		2.2
Varity_R		0.11
gMVP		0.37
Mutation Taster		=86/14	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: rs374699943; hg19: chr8-127568791; COSMIC: COSV59230932; COSMIC: COSV59230932;