1-159808964-T-C

Variant names:

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

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>C​(p.Leu108Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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: not found (cov: 32)
• 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=0.3163028).

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>C	p.Leu108Pro	missense	Exon 4 of 10	NP_001004310.2	Q6DN72-1
	FCRL6	NM_001426231.1		c.353T>C	p.Leu118Pro	missense	Exon 5 of 11	NP_001413160.1
	FCRL6	NM_001426232.1		c.344T>C	p.Leu115Pro	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>C	p.Leu108Pro	missense	Exon 4 of 10	ENSP00000357086.3	Q6DN72-1
	FCRL6	ENST00000339348.9	TSL:1	c.323T>C	p.Leu108Pro	missense	Exon 4 of 9	ENSP00000340949.5	Q6DN72-3
	FCRL6	ENST00000392235.7	TSL:1	c.320-438T>C		intron	N/A	ENSP00000376068.3	Q6DN72-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.078	T
Eigen	Benign	0.13
Eigen_PC	Benign	-0.013
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.3
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.13
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.051	T
Polyphen		1.0	D
Vest4		0.49
MutPred		0.39		Gain of disorder (P = 0.0238)
MVP		0.25
MPC		0.0093
ClinPred		0.95	D
GERP RS		4.2
Varity_R		0.61
gMVP		0.31
Mutation Taster		=84/16	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;