chr12-85280406-T-C

Variant names:

• chr12-85280406-T-C
• rs1243906545
• NM_006982.3:c.145T>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006982.3(ALX1):​c.145T>C​(p.Cys49Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALX1 NM_006982.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.50

Genes affected

ALX1 (HGNC:1494): (ALX homeobox 1) The specific function of this gene has yet to be determined in humans; however, in rodents, it is necessary for survival of the forebrain mesenchyme and may also be involved in development of the cervix. Mutations in the mouse gene lead to neural tube defects such as acrania and meroanencephaly. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.847

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALX1	NM_006982.3	c.145T>C	p.Cys49Arg	missense_variant	Exon 1 of 4	ENST00000316824.4	NP_008913.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALX1	ENST00000316824.4	c.145T>C	p.Cys49Arg	missense_variant	Exon 1 of 4	1	NM_006982.3	ENSP00000315417.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.45
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.084	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.71	T
M_CAP	Pathogenic	0.29	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	0.70	D
MutationAssessor	Benign	1.5	L
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.6	N
REVEL	Pathogenic	0.79
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.34	T
Polyphen		0.98	D
Vest4		0.90
MutPred		0.59		Gain of catalytic residue at K48 (P = 0.0023);
MVP		0.99
MPC		1.2
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.92
gMVP		0.66

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

LitVar

Other links and lift over

dbSNP: rs1243906545; hg19: chr12-85674184;