11-93479122-A-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMCO4	NM_020179.3	c.68T>G	p.Met23Arg	missense_variant	Exon 3 of 3	ENST00000298966.7	NP_064564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMCO4	ENST00000298966.7	c.68T>G	p.Met23Arg	missense_variant	Exon 3 of 3	1	NM_020179.3	ENSP00000298966.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.68T>G (p.M23R) alteration is located in exon 3 (coding exon 1) of the SMCO4 gene. This alteration results from a T to G substitution at nucleotide position 68, causing the methionine (M) at amino acid position 23 to be replaced by an arginine (R). 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	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;T;T;T;T;T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	.;.;.;D;D;D
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.65	D;D;D;D;D;D
MetaSVM	Uncertain	-0.28	T
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.6	D;D;D;.;D;D
REVEL	Uncertain	0.42
Sift	Uncertain	0.023	D;D;D;.;D;D
Sift4G	Uncertain	0.033	D;D;D;D;D;D
Polyphen		0.89	P;P;P;P;.;.
Vest4		0.82
MutPred		0.39		Gain of MoRF binding (P = 0.0268);Gain of MoRF binding (P = 0.0268);Gain of MoRF binding (P = 0.0268);Gain of MoRF binding (P = 0.0268);Gain of MoRF binding (P = 0.0268);Gain of MoRF binding (P = 0.0268);
MVP		0.38
MPC		0.81
ClinPred		0.95	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.69
gMVP		0.84

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: chr11-93212288;