NM_020179.3:c.68T>G

Variant names:

• chr11-93479122-A-C
• NM_020179.3:c.68T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020179.3(SMCO4):​c.68T>G​(p.Met23Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M23T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SMCO4 NM_020179.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.51
• Publications: 0 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 2 ACMG points.

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

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.68T>G	p.Met23Arg	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.68T>G	p.Met23Arg	missense	Exon 3 of 3	ENSP00000298966.2	Q9NRQ5
	SMCO4	ENST00000526869.1	TSL:1	c.68T>G	p.Met23Arg	missense	Exon 3 of 3	ENSP00000435827.1	E9PSB8
	SMCO4	ENST00000525141.1	TSL:2	c.68T>G	p.Met23Arg	missense	Exon 2 of 2	ENSP00000431781.1	Q9NRQ5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.42
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.21	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	-0.28	T
PhyloP100		8.5
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.033	D
Polyphen		0.89	P
Vest4		0.82
MutPred		0.39		Gain of MoRF binding (P = 0.0268)
MVP		0.38
MPC		0.81
ClinPred		0.95	D
GERP RS		6.0
PromoterAI		-0.0040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.69
gMVP		0.84
Mutation Taster		=42/58	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

hg19: chr11-93212288;