chr12-27763013-G-A

Variant names:

• chr12-27763013-G-A
• rs1483805484
• NM_001146221.5:c.748C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001146221.5(MANSC4):​c.748C>T​(p.Pro250Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000857 in 1,399,452 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P250P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000086 (0 hom.)
• Consequence: MANSC4 NM_001146221.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.494
• Publications: 0 publications found

Genes affected

MANSC4 (HGNC:40023): (MANSC domain containing 4) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.025510907).
• BP6: Variant 12-27763013-G-A is Benign according to our data. Variant chr12-27763013-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3869944.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146221.5. 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
	MANSC4	NM_001146221.5	MANE Select	c.748C>T	p.Pro250Ser	missense	Exon 4 of 4	NP_001139693.1	A6NHS7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MANSC4	ENST00000381273.4	TSL:5 MANE Select	c.748C>T	p.Pro250Ser	missense	Exon 4 of 4	ENSP00000370673.3	A6NHS7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000638 AC: 1 AN: 156780 AF XY: 0.0000120

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000165

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000857 AC: 12 AN: 1399452 Hom.: 0 Cov.: 35 AF XY: 0.0000101 AC XY: 7 AN XY: 690228

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.0000102 AC: 11 AN: 1078982

Other (OTH) AF: 0.0000172 AC: 1 AN: 58020

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.060
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.15
DANN	Benign	0.20
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0066	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.9	N
PhyloP100		0.49
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.053
Sift	Benign	0.72	T
Sift4G	Benign	0.79	T
Polyphen		0.0	B
Vest4		0.016
MutPred		0.070		Loss of catalytic residue at P249 (P = 0.0103)
MVP		0.055
ClinPred		0.052	T
GERP RS		-0.70
Varity_R		0.021
gMVP		0.12
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs1483805484; hg19: chr12-27915946;