13-42786784-C-A

Variant names:

• chr13-42786784-C-A
• rs200110453
• NM_001318932.2:c.121C>A

Variant summary

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

The NM_001318932.2(FAM216B):​c.121C>A​(p.Arg41Ser) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R41C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM216B NM_001318932.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.457

Genes affected

FAM216B (HGNC:26883): (family with sequence similarity 216 member B)

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=0.35309517).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM216B	NM_001318932.2	c.121C>A	p.Arg41Ser	missense_variant	Exon 3 of 4	ENST00000313851.3	NP_001305861.1
FAM216B	NM_182508.3	c.121C>A	p.Arg41Ser	missense_variant	Exon 3 of 4		NP_872314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM216B	ENST00000313851.3	c.121C>A	p.Arg41Ser	missense_variant	Exon 3 of 4	1	NM_001318932.2	ENSP00000319336.1
FAM216B	ENST00000537894.5	c.121C>A	p.Arg41Ser	missense_variant	Exon 3 of 4	4		ENSP00000445786.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 11, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.121C>A (p.R41S) alteration is located in exon 3 (coding exon 2) of the FAM216B gene. This alteration results from a C to A substitution at nucleotide position 121, causing the arginine (R) at amino acid position 41 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	Uncertain	0.40
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.66	T;.
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-4.3	D;D
REVEL	Benign	0.15
Sift	Benign	0.49	T;T
Sift4G	Benign	0.60	T;T
Polyphen		0.76	P;P
Vest4		0.56
MutPred		0.30		Loss of MoRF binding (P = 0.0078);Loss of MoRF binding (P = 0.0078);
MVP		0.25
MPC		0.27
ClinPred		0.98	D
GERP RS		-1.1
Varity_R		0.27
gMVP		0.30

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

LitVar

Other links and lift over

dbSNP: rs200110453; hg19: chr13-43360920; COSMIC: COSV58271454;