12-12330515-G-A

Position:

• chr12-12330515-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000535902.6(MANSC1):​c.808C>T​(p.Pro270Ser) 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. 15/21 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. P270L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MANSC1 ENST00000535902.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.679

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045100898).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MANSC1	NM_018050.4	c.808C>T	p.Pro270Ser	missense_variant	4/4	ENST00000535902.6	NP_060520.2
MANSC1	NM_001363613.2	c.706C>T	p.Pro236Ser	missense_variant	5/5		NP_001350542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MANSC1	ENST00000535902.6	c.808C>T	p.Pro270Ser	missense_variant	4/4	1	NM_018050.4	ENSP00000438205.1
MANSC1	ENST00000396349.3	c.706C>T	p.Pro236Ser	missense_variant	5/5	2		ENSP00000379638.3
MANSC1	ENST00000545735.1	c.565C>T	p.Pro189Ser	missense_variant	2/2	2		ENSP00000445303.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 66

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

Feb 14, 2024

The c.808C>T (p.P270S) alteration is located in exon 4 (coding exon 3) of the MANSC1 gene. This alteration results from a C to T substitution at nucleotide position 808, causing the proline (P) at amino acid position 270 to be replaced by a serine (S). 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	0.085
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.4
DANN	Benign	0.85
DEOGEN2	Benign	0.033	T;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.069	N
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.045	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.060
Sift	Benign	0.56	T;T;T
Sift4G	Benign	0.87	T;T;T
Polyphen		0.010	B;.;.
Vest4		0.028
MutPred		0.14		Loss of catalytic residue at P269 (P = 0.0179);.;.;
MVP		0.014
MPC		0.097
ClinPred		0.034	T
GERP RS		-0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.024
gMVP		0.25

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: chr12-12483449;