11-44071274-A-T

Variant names:

• chr11-44071274-A-T
• rs943163475
• NM_032592.4:c.307A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032592.4(ACCS):​c.307A>T​(p.Thr103Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T103A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACCS NM_032592.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18
• Publications: 0 publications found

Genes affected

ACCS (HGNC:23989): (1-aminocyclopropane-1-carboxylate synthase homolog (inactive)) Enables identical protein binding activity. Predicted to be involved in biosynthetic process. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000255165 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032592.4. 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
	ACCS	NM_032592.4	MANE Select	c.307A>T	p.Thr103Ser	missense	Exon 3 of 15	NP_115981.1	A0A0S2Z622
	ACCS	NM_001127219.2		c.307A>T	p.Thr103Ser	missense	Exon 3 of 15	NP_001120691.1	A0A0S2Z622

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACCS	ENST00000263776.9	TSL:1 MANE Select	c.307A>T	p.Thr103Ser	missense	Exon 3 of 15	ENSP00000263776.8	Q96QU6-1
	ACCS	ENST00000527603.5	TSL:1	n.344A>T		non_coding_transcript_exon	Exon 3 of 6
	ACCS	ENST00000894384.1		c.307A>T	p.Thr103Ser	missense	Exon 3 of 15	ENSP00000564443.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Uncertain	0.40	D
MutationAssessor	Benign	2.0	M
PhyloP100		3.2
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.015	D
Polyphen		0.73	P
Vest4		0.33
MutPred		0.68		Gain of disorder (P = 0.0376)
MVP		0.81
MPC		0.36
ClinPred		0.71	D
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.45
Mutation Taster		=76/24	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: rs943163475; hg19: chr11-44092824;