chr11-10306086-G-A

Position:

• chr11-10306086-G-A

Variant summary

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

The NM_001124.3(ADM):​c.236G>A​(p.Ser79Asn) 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADM NM_001124.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.479

Genes affected

ADM (HGNC:259): (adrenomedullin) The protein encoded by this gene is a preprohormone which is cleaved to form two biologically active peptides, adrenomedullin and proadrenomedullin N-terminal 20 peptide. Adrenomedullin is a 52 aa peptide with several functions, including vasodilation, regulation of hormone secretion, promotion of angiogenesis, and antimicrobial activity. The antimicrobial activity is antibacterial, as the peptide has been shown to kill E. coli and S. aureus at low concentration. [provided by RefSeq, Aug 2014]

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=0.051311225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADM	NM_001124.3	c.236G>A	p.Ser79Asn	missense_variant	3/4	ENST00000278175.10	NP_001115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADM	ENST00000278175.10	c.236G>A	p.Ser79Asn	missense_variant	3/4	1	NM_001124.3	ENSP00000278175.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Jan 23, 2024

The c.236G>A (p.S79N) alteration is located in exon 3 (coding exon 2) of the ADM gene. This alteration results from a G to A substitution at nucleotide position 236, causing the serine (S) at amino acid position 79 to be replaced by an asparagine (N). 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	0.086
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	13
DANN	Benign	0.92
DEOGEN2	Benign	0.088	T;T;T;T;T;T;T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.52	.;T;.;.;T;T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.051	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.;.;L;.;L;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.25	N;N;N;N;N;N;N
REVEL	Benign	0.041
Sift	Benign	0.53	T;T;T;T;T;T;T
Sift4G	Benign	0.59	T;T;T;T;T;T;T
Polyphen		0.0010	B;.;.;B;.;B;.
Vest4		0.042
MutPred		0.40		Loss of phosphorylation at S79 (P = 0.0025);.;Loss of phosphorylation at S79 (P = 0.0025);Loss of phosphorylation at S79 (P = 0.0025);Loss of phosphorylation at S79 (P = 0.0025);Loss of phosphorylation at S79 (P = 0.0025);Loss of phosphorylation at S79 (P = 0.0025);
MVP		0.19
MPC		0.48
ClinPred		0.047	T
GERP RS		-0.65
Varity_R		0.041
gMVP		0.091

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: chr11-10327633;