chr1-37794418-A-C

Variant names:

• chr1-37794418-A-C
• rs1401028788
• NM_001113482.2:c.236A>C

Variant summary

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

The NM_001113482.2(MANEAL):​c.236A>C​(p.Asp79Ala) 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MANEAL NM_001113482.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.528
• Publications: 0 publications found

Genes affected

MANEAL (HGNC:26452): (mannosidase endo-alpha like) Predicted to enable alpha-mannosidase activity. Predicted to be located in Golgi membrane. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [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=0.04774019).
• BP6: Variant 1-37794418-A-C is Benign according to our data. Variant chr1-37794418-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2222523.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113482.2. 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
	MANEAL	NM_001113482.2	MANE Select	c.236A>C	p.Asp79Ala	missense	Exon 1 of 4	NP_001106954.1	Q5VSG8-1
	MANEAL	NM_001031740.3		c.236A>C	p.Asp79Ala	missense	Exon 1 of 4	NP_001026910.1	Q5VSG8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MANEAL	ENST00000373045.11	TSL:1 MANE Select	c.236A>C	p.Asp79Ala	missense	Exon 1 of 4	ENSP00000362136.6	Q5VSG8-1
	MANEAL	ENST00000397631.7	TSL:1	c.236A>C	p.Asp79Ala	missense	Exon 1 of 4	ENSP00000380755.3	Q5VSG8-3
	MANEAL	ENST00000951301.1		c.236A>C	p.Asp79Ala	missense	Exon 1 of 5	ENSP00000621360.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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	0.055
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.67
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0041	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.53
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.066
Sift	Benign	0.57	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.063
MutPred		0.10		Gain of methylation at R76 (P = 0.0604)
MVP		0.072
MPC		1.3
ClinPred		0.26	T
GERP RS		0.88
PromoterAI		0.21	Neutral
Varity_R		0.029
gMVP		0.55
Mutation Taster		=92/8	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: rs1401028788; hg19: chr1-38260090;