7-919973-G-C

Variant names:

• chr7-919973-G-C
• rs745515488
• NM_006869.4:c.383C>G

Variant summary

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

The NM_006869.4(ADAP1):​c.383C>G​(p.Ser128Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,453,886 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S128L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ADAP1 NM_006869.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.14
• Publications: 0 publications found

Genes affected

ADAP1 (HGNC:16486): (ArfGAP with dual PH domains 1) Enables GTPase activator activity. Involved in regulation of GTPase activity. Located in cytosol; nucleus; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

COX19 (HGNC:28074): (cytochrome c oxidase assembly factor COX19) COX19 encodes a cytochrome c oxidase (COX)-assembly protein. The S. cerevisiae Cox19 protein may play a role in metal transport to the mitochondrial intermembrane space and assembly of complex IV of the mitochondrial respiratory chain (Sacconi et al., 2005 [PubMed 16212937]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006869.4. 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
	ADAP1	NM_006869.4	MANE Select	c.383C>G	p.Ser128Trp	missense	Exon 4 of 11	NP_006860.2	O75689-1
	ADAP1	NM_001284308.2		c.416C>G	p.Ser139Trp	missense	Exon 4 of 11	NP_001271237.2	O75689-2
	ADAP1	NM_001284309.2		c.167C>G	p.Ser56Trp	missense	Exon 4 of 11	NP_001271238.2	O75689-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAP1	ENST00000265846.10	TSL:1 MANE Select	c.383C>G	p.Ser128Trp	missense	Exon 4 of 11	ENSP00000265846.5	O75689-1
	ADAP1	ENST00000539900.5	TSL:2	c.416C>G	p.Ser139Trp	missense	Exon 4 of 11	ENSP00000442682.1	O75689-2
	ADAP1	ENST00000943017.1		c.383C>G	p.Ser128Trp	missense	Exon 4 of 11	ENSP00000613076.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453886 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 723388

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111428

Other (OTH) AF: 0.00 AC: 0 AN: 60264

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	32
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		4.1
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.39		Loss of disorder (P = 0.0067)
MVP		0.33
MPC		1.4
ClinPred		0.98	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.38
gMVP		0.68
Mutation Taster		=36/64	disease causing

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: rs745515488; hg19: chr7-959610;