3-196508300-T-C

Position:

• chr3-196508300-T-C

Variant summary

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

The NM_001077657.3(SMCO1):​c.232A>G​(p.Ser78Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMCO1 NM_001077657.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.95

Genes affected

SMCO1 (HGNC:27407): (single-pass membrane protein with coiled-coil domains 1) Predicted to be integral component of membrane. [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=0.19459784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMCO1	NM_001077657.3	c.232A>G	p.Ser78Gly	missense_variant	3/3	ENST00000397537.3
SMCO1	NM_001320473.2	c.208A>G	p.Ser70Gly	missense_variant	3/3
SMCO1	XM_024453435.2	c.226A>G	p.Ser76Gly	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMCO1	ENST00000397537.3	c.232A>G	p.Ser78Gly	missense_variant	3/3	1	NM_001077657.3	P1
SMCO1	ENST00000452776.1	c.*177A>G		3_prime_UTR_variant, NMD_transcript_variant	3/3	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 17, 2023

The c.232A>G (p.S78G) alteration is located in exon 3 (coding exon 3) of the SMCO1 gene. This alteration results from a A to G substitution at nucleotide position 232, causing the serine (S) at amino acid position 78 to be replaced by a glycine (G). 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	Benign	0.18
BayesDel_addAF	Benign	-0.0042	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.081
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	0.93	D
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.16
Sift	Benign	0.11	T
Sift4G	Benign	0.17	T
Polyphen		0.19	B
Vest4		0.54
MutPred		0.29		Loss of sheet (P = 0.0457);
MVP		0.25
MPC		0.79
ClinPred		0.79	D
GERP RS		4.3
Varity_R		0.15
gMVP		0.13

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: chr3-196235171;