11-93479029-C-G

Variant names:

• chr11-93479029-C-G
• rs757684648
• NM_020179.3:c.161G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020179.3(SMCO4):​c.161G>C​(p.Arg54Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R54C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SMCO4 NM_020179.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.49
• Publications: 1 publications found

Genes affected

SMCO4 (HGNC:24810): (single-pass membrane protein with coiled-coil domains 4) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.768

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020179.3. 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
	SMCO4	NM_020179.3	MANE Select	c.161G>C	p.Arg54Pro	missense	Exon 3 of 3	NP_064564.1	Q9NRQ5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMCO4	ENST00000298966.7	TSL:1 MANE Select	c.161G>C	p.Arg54Pro	missense	Exon 3 of 3	ENSP00000298966.2	Q9NRQ5
	SMCO4	ENST00000525141.1	TSL:2	c.161G>C	p.Arg54Pro	missense	Exon 2 of 2	ENSP00000431781.1	Q9NRQ5
	SMCO4	ENST00000527149.5	TSL:5	c.161G>C	p.Arg54Pro	missense	Exon 3 of 3	ENSP00000433555.1	Q9NRQ5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 74

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.36
CADD	Pathogenic	26
DANN	Benign	0.97
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.042	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.61	T
PhyloP100		5.5
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.98	D
Vest4		0.93
MutPred		0.35		Gain of glycosylation at P55 (P = 0.0807)
MVP		0.26
MPC		0.77
ClinPred		0.98	D
GERP RS		5.0
PromoterAI		0.051	Neutral
Varity_R		0.88
gMVP		0.97
Mutation Taster		=49/51	disease causing

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

Other links and lift over

dbSNP: rs757684648; hg19: chr11-93212195;