chr12-12330241-T-G

Variant names:

• chr12-12330241-T-G
• NM_018050.4:c.1082A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018050.4(MANSC1):​c.1082A>C​(p.Glu361Ala) 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. 16/22 in silico tools predict a benign outcome for this variant. 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. E361D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MANSC1 NM_018050.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.229
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055625916).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018050.4. 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
	MANSC1	NM_018050.4	MANE Select	c.1082A>C	p.Glu361Ala	missense	Exon 4 of 4	NP_060520.2
	MANSC1	NM_001363613.2		c.980A>C	p.Glu327Ala	missense	Exon 5 of 5	NP_001350542.1	Q9H8J5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MANSC1	ENST00000535902.6	TSL:1 MANE Select	c.1082A>C	p.Glu361Ala	missense	Exon 4 of 4	ENSP00000438205.1	Q9H8J5-1
	MANSC1	ENST00000938078.1		c.1082A>C	p.Glu361Ala	missense	Exon 4 of 4	ENSP00000608137.1
	MANSC1	ENST00000938079.1		c.1082A>C	p.Glu361Ala	missense	Exon 4 of 4	ENSP00000608138.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Benign	0.088
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.94
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.084	N
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.23
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.010
Sift	Benign	0.32	T
Sift4G	Benign	0.63	T
Polyphen		0.039	B
Vest4		0.067
MutPred		0.14		Gain of MoRF binding (P = 0.0597)
MVP		0.040
MPC		0.10
ClinPred		0.060	T
GERP RS		2.3
Varity_R		0.037
gMVP		0.099
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr12-12483175;