NM_139164.3:c.419A>G

Variant names:

• chr5-111500085-T-C
• NM_139164.3:c.419A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_139164.3(STARD4):​c.419A>G​(p.Glu140Gly) variant causes a missense change. 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: 32)
• Consequence: STARD4 NM_139164.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.67
• Publications: 0 publications found

Genes affected

STARD4 (HGNC:18058): (StAR related lipid transfer domain containing 4) Cholesterol homeostasis is regulated, at least in part, by sterol regulatory element (SRE)-binding proteins (e.g., SREBP1; MIM 184756) and by liver X receptors (e.g., LXRA; MIM 602423). Upon sterol depletion, LXRs are inactive and SREBPs are cleaved, after which they bind promoter SREs and activate genes involved in cholesterol biosynthesis and uptake. Sterol transport is mediated by vesicles or by soluble protein carriers, such as steroidogenic acute regulatory protein (STAR; MIM 600617). STAR is homologous to a family of proteins containing a 200- to 210-amino acid STAR-related lipid transfer (START) domain, including STARD4 (Soccio et al., 2002 [PubMed 12011452]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28356445).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139164.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STARD4	NM_139164.3	MANE Select	c.419A>G	p.Glu140Gly	missense	Exon 6 of 6	NP_631903.1	Q96DR4-1
	STARD4	NM_001308056.2		c.419A>G	p.Glu140Gly	missense	Exon 6 of 6	NP_001294985.1	Q96DR4-1
	STARD4	NM_001308059.2		c.173A>G	p.Glu58Gly	missense	Exon 7 of 7	NP_001294988.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STARD4	ENST00000296632.8	TSL:2 MANE Select	c.419A>G	p.Glu140Gly	missense	Exon 6 of 6	ENSP00000296632.3	Q96DR4-1
	STARD4	ENST00000505803.5	TSL:2	c.419A>G	p.Glu140Gly	missense	Exon 6 of 6	ENSP00000427478.2	Q96DR4-1
	STARD4	ENST00000925892.1		c.419A>G	p.Glu140Gly	missense	Exon 6 of 6	ENSP00000595951.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.7
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.11
Sift	Benign	0.094	T
Sift4G	Benign	0.082	T
Polyphen		0.88	P
Vest4		0.29
MutPred		0.37		Loss of solvent accessibility (P = 0.0387)
MVP		0.71
MPC		0.19
ClinPred		0.88	D
GERP RS		5.7
Varity_R		0.27
gMVP		0.58
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr5-110835783;