12-12330119-C-G

Variant names:

• chr12-12330119-C-G
• NM_018050.4:c.1204G>C

Variant summary

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

The NM_018050.4(MANSC1):​c.1204G>C​(p.Val402Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: MANSC1 NM_018050.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284

Genes affected

MANSC1 (HGNC:25505): (MANSC domain containing 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=0.16549203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MANSC1	NM_018050.4	c.1204G>C	p.Val402Leu	missense_variant	Exon 4 of 4	ENST00000535902.6	NP_060520.2
MANSC1	NM_001363613.2	c.1102G>C	p.Val368Leu	missense_variant	Exon 5 of 5		NP_001350542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MANSC1	ENST00000535902.6	c.1204G>C	p.Val402Leu	missense_variant	Exon 4 of 4	1	NM_018050.4	ENSP00000438205.1
MANSC1	ENST00000396349.3	c.1102G>C	p.Val368Leu	missense_variant	Exon 5 of 5	2		ENSP00000379638.3
MANSC1	ENST00000545735.1	c.961G>C	p.Val321Leu	missense_variant	Exon 2 of 2	2		ENSP00000445303.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461678 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727144

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	10
DANN	Benign	0.95
DEOGEN2	Benign	0.11	T;.;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.061	N
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.070
Sift	Uncertain	0.018	D;D;T
Sift4G	Benign	0.081	T;T;T
Polyphen		0.81	P;.;.
Vest4		0.23
MutPred		0.34		Loss of sheet (P = 0.0457);.;.;
MVP		0.014
MPC		0.12
ClinPred		0.26	T
GERP RS		0.81
Varity_R		0.12
gMVP		0.62

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: chr12-12483053;