chr1-27551779-T-A

Variant names:

• chr1-27551779-T-A
• rs1135401946
• NM_001371928.1:c.337A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001029882.3(AHDC1):​c.337A>T​(p.Asn113Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. N113N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AHDC1 NM_001029882.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.40
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 1-27551779-T-A is Benign according to our data. Variant chr1-27551779-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 431372.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001029882.3. 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
	AHDC1	NM_001371928.1	MANE Select	c.337A>T	p.Asn113Tyr	missense	Exon 8 of 9	NP_001358857.1
	AHDC1	NM_001029882.3		c.337A>T	p.Asn113Tyr	missense	Exon 6 of 7	NP_001025053.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHDC1	ENST00000673934.1	MANE Select	c.337A>T	p.Asn113Tyr	missense	Exon 8 of 9	ENSP00000501218.1
	AHDC1	ENST00000247087.10	TSL:5	c.337A>T	p.Asn113Tyr	missense	Exon 5 of 6	ENSP00000247087.4
	AHDC1	ENST00000374011.6	TSL:5	c.337A>T	p.Asn113Tyr	missense	Exon 6 of 7	ENSP00000363123.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.035	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.56	T
M_CAP	Uncertain	0.25	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.55	N
PhyloP100		2.4
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.64	T
Polyphen		1.0	D
Vest4		0.76
MutPred		0.57		Loss of solvent accessibility (P = 0.0174)
MVP		0.20
MPC		1.6
ClinPred		0.84	D
GERP RS		4.0
Varity_R		0.29
gMVP		0.55
Mutation Taster		=81/19	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: rs1135401946; hg19: chr1-27878290;