chr1-159808964-T-G

Variant names:

• chr1-159808964-T-G
• rs149327737
• NM_001004310.3:c.323T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001004310.3(FCRL6):​c.323T>G​(p.Leu108Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,046 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L108Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FCRL6 NM_001004310.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33889747).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004310.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRL6	NM_001004310.3	MANE Select	c.323T>G	p.Leu108Arg	missense	Exon 4 of 10	NP_001004310.2	Q6DN72-1
	FCRL6	NM_001426231.1		c.353T>G	p.Leu118Arg	missense	Exon 5 of 11	NP_001413160.1
	FCRL6	NM_001426232.1		c.344T>G	p.Leu115Arg	missense	Exon 5 of 11	NP_001413161.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRL6	ENST00000368106.4	TSL:1 MANE Select	c.323T>G	p.Leu108Arg	missense	Exon 4 of 10	ENSP00000357086.3	Q6DN72-1
	FCRL6	ENST00000339348.9	TSL:1	c.323T>G	p.Leu108Arg	missense	Exon 4 of 9	ENSP00000340949.5	Q6DN72-3
	FCRL6	ENST00000392235.7	TSL:1	c.320-438T>G		intron	N/A	ENSP00000376068.3	Q6DN72-4

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152046 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1450984 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 721108

African (AFR) AF: 0.00 AC: 0 AN: 33230

American (AMR) AF: 0.00 AC: 0 AN: 43704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25198

East Asian (EAS) AF: 0.00 AC: 0 AN: 39520

South Asian (SAS) AF: 0.00 AC: 0 AN: 84852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52966

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105944

Other (OTH) AF: 0.00 AC: 0 AN: 59868

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152046 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74278

African (AFR) AF: 0.00 AC: 0 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15284

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67968

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.081	T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.055
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		1.3
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.13
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.61
MutPred		0.37		Gain of disorder (P = 0.0545)
MVP		0.36
MPC		0.043
ClinPred		0.99	D
GERP RS		4.2
Varity_R		0.62
gMVP		0.23
Mutation Taster		=83/17	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: rs149327737; hg19: chr1-159778754;