1-27552016-T-C

Variant names:

• chr1-27552016-T-C
• rs758473342
• NM_001371928.1:c.100A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001371928.1(AHDC1):​c.100A>G​(p.Thr34Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 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. T34P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AHDC1 NM_001371928.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 5 publications found

Genes affected

AHDC1 (HGNC:25230): (AT-hook DNA binding motif containing 1) This gene encodes a protein containing two AT-hooks, which likely function in DNA binding. Mutations in this gene were found in individuals with Xia-Gibbs syndrome. [provided by RefSeq, Jun 2014]

AHDC1 Gene-Disease associations (from GenCC):

• AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Orphanet, G2P, ClinGen

ENSG00000300470 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.056669563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHDC1	NM_001371928.1	c.100A>G	p.Thr34Ala	missense_variant	Exon 8 of 9	ENST00000673934.1	NP_001358857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHDC1	ENST00000673934.1	c.100A>G	p.Thr34Ala	missense_variant	Exon 8 of 9		NM_001371928.1	ENSP00000501218.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 21662 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 53166 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 25834

African (AFR) AF: 0.00 AC: 0 AN: 1216

American (AMR) AF: 0.00 AC: 0 AN: 1082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 690

East Asian (EAS) AF: 0.00 AC: 0 AN: 812

South Asian (SAS) AF: 0.00 AC: 0 AN: 2988

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2246

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 168

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 41896

Other (OTH) AF: 0.00 AC: 0 AN: 2068

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 21662 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10062

African (AFR) AF: 0.00 AC: 0 AN: 5730

American (AMR) AF: 0.00 AC: 0 AN: 2018

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 586

East Asian (EAS) AF: 0.00 AC: 0 AN: 522

South Asian (SAS) AF: 0.00 AC: 0 AN: 528

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 42

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 10710

Other (OTH) AF: 0.00 AC: 0 AN: 238

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.026	T;T;T;T;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.0	.;.;T;.;.
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.057	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N;N;N;N
PhyloP100		2.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.43	N;.;N;.;.
REVEL	Benign	0.079
Sift	Benign	0.23	T;.;T;.;.
Sift4G	Benign	0.32	T;.;T;.;.
Vest4		0.11
ClinPred		0.18	T
GERP RS		0.51
Varity_R		0.070
gMVP		0.10
Mutation Taster		=98/2	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: rs758473342; hg19: chr1-27878527;