1-37794418-A-C

Position:

• chr1-37794418-A-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The ENST00000373045.11(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. 14/20 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 ENST00000373045.11 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.528

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

Verdict is Likely_benign. Variant got -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 id is 2222523.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MANEAL	NM_001113482.2	c.236A>C	p.Asp79Ala	missense_variant	1/4	ENST00000373045.11	NP_001106954.1
MANEAL	NM_001031740.3	c.236A>C	p.Asp79Ala	missense_variant	1/4		NP_001026910.1
MANEAL	XM_005270510.4	c.236A>C	p.Asp79Ala	missense_variant	1/3		XP_005270567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MANEAL	ENST00000373045.11	c.236A>C	p.Asp79Ala	missense_variant	1/4	1	NM_001113482.2	ENSP00000362136.6
MANEAL	ENST00000397631.7	c.236A>C	p.Asp79Ala	missense_variant	1/4	1		ENSP00000380755.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.048	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.37	N;N
REVEL	Benign	0.066
Sift	Benign	0.57	T;T
Sift4G	Benign	0.55	T;T
Polyphen		0.0	B;B
Vest4		0.063
MutPred		0.10		Gain of methylation at R76 (P = 0.0604);Gain of methylation at R76 (P = 0.0604);
MVP		0.072
MPC		1.3
ClinPred		0.26	T
GERP RS		0.88
Varity_R		0.029
gMVP		0.55

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: chr1-38260090;