6-3850302-G-C

Variant names:

• chr6-3850302-G-C
• NM_012135.3:c.491G>C

Variant summary

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

The NM_012135.3(FAM50B):​c.491G>C​(p.Arg164Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,970 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAM50B NM_012135.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.26

Genes affected

FAM50B (HGNC:18789): (family with sequence similarity 50 member B) This gene contains an intronless ORF that arose from ancestral retroposition. The encoded protein is related to a plant protein that plays a role in the circadian clock. This gene is adjacent to a differentially methylated region (DMR) and is imprinted and paternally expressed in many tissues. [provided by RefSeq, Nov 2015]

ENSG00000238158 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM50B	NM_012135.3	c.491G>C	p.Arg164Pro	missense_variant	Exon 2 of 2	ENST00000648326.1	NP_036267.1
FAM50B	XM_017010729.2	c.491G>C	p.Arg164Pro	missense_variant	Exon 2 of 2		XP_016866218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM50B	ENST00000648326.1	c.491G>C	p.Arg164Pro	missense_variant	Exon 2 of 2		NM_012135.3	ENSP00000496837.1
FAM50B	ENST00000380274.2	c.491G>C	p.Arg164Pro	missense_variant	Exon 1 of 1	6		ENSP00000369627.1
ENSG00000238158	ENST00000454396.2	n.80-5168G>C		intron_variant	Intron 1 of 1	5
ENSG00000233068	ENST00000648025.1	n.76+18291G>C		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460970 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726798

Gnomad4 AFR exome AF: 0.0000299

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.491G>C (p.R164P) alteration is located in exon 2 (coding exon 1) of the FAM50B gene. This alteration results from a G to C substitution at nucleotide position 491, causing the arginine (R) at amino acid position 164 to be replaced by a proline (P). 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	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;T;T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Pathogenic	0.98	.;.;D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.7	M;M;M
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-4.4	.;D;D
REVEL	Benign	0.26
Sift	Benign	0.042	.;D;D
Sift4G	Benign	0.17	.;T;T
Polyphen		0.98	D;D;D
Vest4		0.40, 0.45
MutPred		0.52		Loss of helix (P = 0.0304);Loss of helix (P = 0.0304);Loss of helix (P = 0.0304);
MVP		0.62
MPC		2.2
ClinPred		0.99	D
GERP RS		4.1
Varity_R		0.87
gMVP		0.78

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: chr6-3850536;