chr4-17632593-T-C

Variant names:

• chr4-17632593-T-C
• rs916540890
• NM_015688.2:c.3122A>G

Variant summary

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

The NM_015688.2(FAM184B):​c.3122A>G​(p.Glu1041Gly) 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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: FAM184B NM_015688.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58

Genes affected

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

MED28 (HGNC:24628): (mediator complex subunit 28) Predicted to enable actin binding activity. Predicted to act upstream of or within negative regulation of smooth muscle cell differentiation and stem cell population maintenance. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.09318724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM184B	NM_015688.2	c.3122A>G	p.Glu1041Gly	missense_variant	Exon 18 of 18	ENST00000265018.4	NP_056503.1
MED28	NM_025205.5	c.*8795T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000237380.12	NP_079481.2
FAM184B	XM_047450066.1	c.*807A>G		3_prime_UTR_variant	Exon 17 of 17		XP_047306022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM184B	ENST00000265018.4	c.3122A>G	p.Glu1041Gly	missense_variant	Exon 18 of 18	1	NM_015688.2	ENSP00000265018.3
MED28	ENST00000237380.12	c.*8795T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_025205.5	ENSP00000237380.6
MED28	ENST00000499786.4	n.*154T>C		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.061
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.022	D
Polyphen		0.99	D
Vest4		0.16
MutPred		0.13		Gain of loop (P = 0.0312);
MVP		0.17
ClinPred		0.93	D
GERP RS		5.5
Varity_R		0.15
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs916540890; hg19: chr4-17634216;