5-192160-G-T

Variant names:

• chr5-192160-G-T
• NM_001080478.3:c.622G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001080478.3(LRRC14B):​c.622G>T​(p.Ala208Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000208 in 1,444,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LRRC14B NM_001080478.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.83

Genes affected

LRRC14B (HGNC:37268): (leucine rich repeat containing 14B) The protein encoded by this gene is a leucine-rich repeat containing protein that is a member of the PRAME family. [provided by RefSeq, Apr 2017]

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=0.29631132).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC14B	NM_001080478.3	c.622G>T	p.Ala208Ser	missense_variant	Exon 1 of 2	ENST00000328278.4	NP_001073947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC14B	ENST00000328278.4	c.622G>T	p.Ala208Ser	missense_variant	Exon 1 of 2	1	NM_001080478.3	ENSP00000327675.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1444944 Hom.: 0 Cov.: 32 AF XY: 0.00000418 AC XY: 3 AN XY: 717204

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: 0.00000271

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

Jan 15, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.622G>T (p.A208S) alteration is located in exon 1 (coding exon 1) of the LRRC14B gene. This alteration results from a G to T substitution at nucleotide position 622, causing the alanine (A) at amino acid position 208 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	Benign	0.16
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.13
Sift	Benign	0.082	T
Sift4G	Uncertain	0.025	D
Polyphen		0.65	P
Vest4		0.32
MutPred		0.31		Gain of disorder (P = 0.0411);
MVP		0.39
MPC		0.50
ClinPred		0.94	D
GERP RS		5.2
Varity_R		0.17
gMVP		0.46

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: chr5-192275;