12-95966728-T-C

Variant names:

• chr12-95966728-T-C
• rs1025607
• NM_152435.3:c.1193+220T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152435.3(AMDHD1):​c.1193+220T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 152,102 control chromosomes in the GnomAD database, including 33,865 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.67 (33865 hom., cov: 32)
• Consequence: AMDHD1 NM_152435.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372
• Publications: 8 publications found

Genes affected

AMDHD1 (HGNC:28577): (amidohydrolase domain containing 1) Predicted to enable imidazolonepropionase activity. Predicted to be involved in histidine catabolic process. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMDHD1	NM_152435.3	c.1193+220T>C		intron_variant	Intron 8 of 8	ENST00000266736.7	NP_689648.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMDHD1	ENST00000266736.7	c.1193+220T>C		intron_variant	Intron 8 of 8	1	NM_152435.3	ENSP00000266736.2
AMDHD1	ENST00000548310.1	n.*672+220T>C		intron_variant	Intron 7 of 7	1		ENSP00000448632.1

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101066 AN: 151984 Hom.: 33827 Cov.: 32

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.663

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.665 AC: 101155 AN: 152102 Hom.: 33865 Cov.: 32 AF XY: 0.662 AC XY: 49252 AN XY: 74346

African (AFR) AF: 0.745 AC: 30893 AN: 41484

American (AMR) AF: 0.690 AC: 10540 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2318 AN: 3464

East Asian (EAS) AF: 0.554 AC: 2863 AN: 5170

South Asian (SAS) AF: 0.567 AC: 2731 AN: 4820

European-Finnish (FIN) AF: 0.607 AC: 6414 AN: 10574

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.637 AC: 43284 AN: 67992

Other (OTH) AF: 0.661 AC: 1394 AN: 2110

Alfa AF: 0.637 Hom.: 15618

Bravo AF: 0.677

Asia WGS AF: 0.564 AC: 1959 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.4
DANN	Benign	0.46
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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: rs1025607; hg19: chr12-96360506;