rs116999073

Positions:

• chr11-64116674-A-C
• chr11-64116674-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000255681.7(MACROD1):​c.517+34565T>G variant causes a intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MACROD1 ENST00000255681.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.50

Genes affected

FLRT1 (HGNC:3760): (fibronectin leucine rich transmembrane protein 1) This gene encodes a member of the fibronectin leucine rich transmembrane protein (FLRT) family. The family members may function in cell adhesion and/or receptor signalling. Their protein structures resemble small leucine-rich proteoglycans found in the extracellular matrix. The encoded protein shares sequence similarity with two other family members, FLRT2 and FLRT3. This gene is expressed in kidney and brain. [provided by RefSeq, Jul 2008]

MACROD1 (HGNC:29598): (mono-ADP ribosylhydrolase 1) Enables ADP-ribosylglutamate hydrolase activity and deacetylase activity. Involved in cellular response to DNA damage stimulus; peptidyl-glutamate ADP-deribosylation; and purine nucleoside metabolic process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLRT1	NM_013280.5	c.407A>C	p.Asp136Ala	missense_variant	3/3	ENST00000682287.1	NP_037412.2
MACROD1	NM_014067.4	c.517+34565T>G		intron_variant		ENST00000255681.7	NP_054786.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLRT1	ENST00000682287.1	c.407A>C	p.Asp136Ala	missense_variant	3/3		NM_013280.5	ENSP00000507207	P1
MACROD1	ENST00000255681.7	c.517+34565T>G		intron_variant		1	NM_014067.4	ENSP00000255681	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 84

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Benign	23
DANN	Uncertain	1.0
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.80	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.043	D
Vest4		0.73
MVP		0.43
MPC		0.75
ClinPred		0.98	D
GERP RS		4.4
gMVP		0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs116999073; hg19: chr11-63884146;