NM_001082486.2:c.801C>G

Variant names:

• chr16-67658583-G-C
• rs72549181
• NM_001082486.2:c.801C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001082486.2(ACD):​c.801C>G​(p.Ala267Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A267A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ACD NM_001082486.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.412
• Publications: 0 publications found

Genes affected

ACD (HGNC:25070): (ACD shelterin complex subunit and telomerase recruitment factor) This gene encodes a protein that is involved in telomere function. This protein is one of six core proteins in the telosome/shelterin telomeric complex, which functions to maintain telomere length and to protect telomere ends. Through its interaction with other components, this protein plays a key role in the assembly and stabilization of this complex, and it mediates the access of telomerase to the telomere. Multiple transcript variants encoding different isoforms have been found for this gene. This gene, which is also referred to as TPP1, is distinct from the unrelated TPP1 gene on chromosome 11, which encodes tripeptidyl-peptidase I. [provided by RefSeq, Jul 2008]

ACD Gene-Disease associations (from GenCC):

• ACD-related short telomere syndrome

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
• dyskeratosis congenita, autosomal dominant 6

  Inheritance: AR, AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P
• hereditary isolated aplastic anemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Hoyeraal-Hreidarsson syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-67658583-G-C is Benign according to our data. Variant chr16-67658583-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1779435.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.412 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001082486.2. 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
	ACD	NM_001082486.2	MANE Select	c.801C>G	p.Ala267Ala	synonymous	Exon 9 of 12	NP_001075955.2	Q96AP0-3
	ACD	NM_022914.3		c.792C>G	p.Ala264Ala	synonymous	Exon 9 of 12	NP_075065.3	Q96AP0-2
	ACD	NM_001410884.1		c.742+137C>G		intron	N/A	NP_001397813.1	A0A8Q3WM11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACD	ENST00000620761.6	TSL:1 MANE Select	c.801C>G	p.Ala267Ala	synonymous	Exon 9 of 12	ENSP00000478084.1	Q96AP0-3
	ACD	ENST00000695659.1		c.801C>G	p.Ala267Ala	synonymous	Exon 9 of 12	ENSP00000512089.1	A0A8Q3SHY1
	ACD	ENST00000219251.13	TSL:2	c.792C>G	p.Ala264Ala	synonymous	Exon 9 of 12	ENSP00000219251.8	Q96AP0-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.4
DANN	Benign	0.62
PhyloP100		-0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs72549181; hg19: chr16-67692486;