15-49541730-T-G

Variant summary

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

The NM_152647.3(FAM227B):c.824A>C(p.Asn275Thr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM227B NM_152647.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.58

Genes affected

FAM227B (HGNC:26543): (family with sequence similarity 227 member B)

LOC105370811 (HGNC:):

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=0.23967308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM227B	NM_152647.3	c.824A>C	p.Asn275Thr	missense_variant	10/16	ENST00000299338.11
LOC105370811	XR_001751537.2	n.88+3269T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM227B	ENST00000299338.11	c.824A>C	p.Asn275Thr	missense_variant	10/16	2	NM_152647.3	P1
FAM227B	ENST00000561064.5	c.722A>C	p.Asn241Thr	missense_variant	9/11	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Jun 12, 2023

The c.824A>C (p.N275T) alteration is located in exon 10 (coding exon 9) of the FAM227B gene. This alteration results from a A to C substitution at nucleotide position 824, causing the asparagine (N) at amino acid position 275 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	0.17
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	20
Dann	Uncertain	1.0
DEOGEN2	Benign	0.021	T;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	0.79	D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.5	N;D
REVEL	Benign	0.063
Sift	Benign	0.40	T;T
Sift4G	Uncertain	0.011	D;D
Polyphen		0.63	P;D
Vest4		0.39
MutPred		0.31		Gain of helix (P = 0.0854);.;
MVP		0.067
MPC		0.10
ClinPred		0.89	D
GERP RS		5.7
Varity_R		0.17
gMVP		0.098

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: chr15-49833927;