chr1-159809465-T-C

Position:

• chr1-159809465-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004310.3(FCRL6):​c.668T>C​(p.Met223Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FCRL6 NM_001004310.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.44

Genes affected

FCRL6 (HGNC:31910): (Fc receptor like 6) Enables MHC class II protein binding activity and protein phosphatase binding activity. Predicted to be involved in cell surface receptor signaling pathway. Located in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07333967).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCRL6	NM_001004310.3	c.668T>C	p.Met223Thr	missense_variant	5/10	ENST00000368106.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCRL6	ENST00000368106.4	c.668T>C	p.Met223Thr	missense_variant	5/10	1	NM_001004310.3	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461742 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727168

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Dec 12, 2023

The c.668T>C (p.M223T) alteration is located in exon 5 (coding exon 5) of the FCRL6 gene. This alteration results from a T to C substitution at nucleotide position 668, causing the methionine (M) at amino acid position 223 to be replaced by a threonine (T). 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	0.077
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.010
DANN	Benign	0.23
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.30	T;T;T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.073	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.45	N;N;N;N
REVEL	Benign	0.0070
Sift	Benign	0.62	T;T;T;T
Sift4G	Benign	0.19	T;T;T;T
Polyphen		0.0040	B;B;B;B
Vest4		0.076
MutPred		0.48		.;Gain of phosphorylation at M223 (P = 0.0613);.;Gain of phosphorylation at M223 (P = 0.0613);
MVP		0.014
MPC		0.0084
ClinPred		0.039	T
GERP RS		-4.0
Varity_R		0.060
gMVP		0.12

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: chr1-159779255;