chr4-17635096-G-C

Position:

• chr4-17635096-G-C

Variant summary

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

The NM_015688.2(FAM184B):​c.2802C>G​(p.His934Gln) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM184B NM_015688.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00200

Genes affected

FAM184B (HGNC:29235): (family with sequence similarity 184 member B)

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=0.07365167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM184B	NM_015688.2	c.2802C>G	p.His934Gln	missense_variant	16/18	ENST00000265018.4	NP_056503.1
FAM184B	XM_047450066.1	c.2802C>G	p.His934Gln	missense_variant	16/17		XP_047306022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM184B	ENST00000265018.4	c.2802C>G	p.His934Gln	missense_variant	16/18	1	NM_015688.2	ENSP00000265018.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

May 08, 2024

The c.2802C>G (p.H934Q) alteration is located in exon 16 (coding exon 16) of the FAM184B gene. This alteration results from a C to G substitution at nucleotide position 2802, causing the histidine (H) at amino acid position 934 to be replaced by a glutamine (Q). 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	0.28
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	6.8
DANN	Benign	0.79
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.036
Sift	Benign	0.25	T
Sift4G	Benign	0.53	T
Polyphen		0.018	B
Vest4		0.14
MutPred		0.25		Gain of glycosylation at Y935 (P = 0.0582);
MVP		0.030
ClinPred		0.23	T
GERP RS		2.2
Varity_R		0.10
gMVP		0.27

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: chr4-17636719;