1-173659271-C-G

Variant names:

• chr1-173659271-C-G
• rs775112392
• NM_198493.3:c.148G>C

Variant summary

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

The NM_198493.3(ANKRD45):​c.148G>C​(p.Gly50Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G50S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKRD45 NM_198493.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.94
• Publications: 0 publications found

Genes affected

ANKRD45 (HGNC:24786): (ankyrin repeat domain 45)

ENSG00000285777 (HGNC:):

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_198493.3. 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
	ANKRD45	NM_198493.3	MANE Select	c.148G>C	p.Gly50Arg	missense	Exon 2 of 6	NP_940895.1	Q5TZF3-2
	ANKRD45	NR_158771.1		n.198G>C		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD45	ENST00000333279.3	TSL:1 MANE Select	c.148G>C	p.Gly50Arg	missense	Exon 2 of 6	ENSP00000331268.2	Q5TZF3-2
	ANKRD45	ENST00000367712.2	TSL:1	n.179G>C		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000285777	ENST00000648193.1		n.148G>C		non_coding_transcript_exon	Exon 2 of 8	ENSP00000498204.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0091	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0055	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.9
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.17	N
REVEL	Benign	0.16
Sift	Benign	0.80	T
Sift4G	Uncertain	0.051	T
Vest4		0.64
MVP		0.73
MPC		0.20
ClinPred		0.69	D
GERP RS		2.6
Varity_R		0.048
gMVP		0.61
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs775112392; hg19: chr1-173628410;