rs370628862

Variant names:

• chr1-37795801-C-A
• NM_001113482.2:c.615C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-37795801-C-A
• chr1-37795801-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001113482.2(MANEAL):​c.615C>A​(p.Asp205Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D205D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MANEAL NM_001113482.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19404906).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MANEAL	NM_001113482.2	c.615C>A	p.Asp205Glu	missense_variant	Exon 2 of 4	ENST00000373045.11	NP_001106954.1
MANEAL	NM_001031740.3	c.615C>A	p.Asp205Glu	missense_variant	Exon 2 of 4		NP_001026910.1
MANEAL	NM_152496.3	c.26C>A	p.Thr9Asn	missense_variant	Exon 1 of 2		NP_689709.1
MANEAL	XM_005270510.4	c.615C>A	p.Asp205Glu	missense_variant	Exon 2 of 3		XP_005270567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MANEAL	ENST00000373045.11	c.615C>A	p.Asp205Glu	missense_variant	Exon 2 of 4	1	NM_001113482.2	ENSP00000362136.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461866 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.054	T;.;T;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.70	T;T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-0.93	T
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.2	N;N;N;N
REVEL	Uncertain	0.42
Sift	Benign	0.22	T;T;T;T
Sift4G	Benign	0.30	T;T;T;T
Polyphen		0.098	B;D;.;.
Vest4		0.30
MutPred		0.23		Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);.;.;
MVP		0.82
MPC		1.2
ClinPred		0.98	D
GERP RS		0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.45

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: chr1-38261473;