1-173659271-C-G

Position:

• chr1-173659271-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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

Genes affected

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

(HGNC:):

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
ANKRD45	NM_198493.3	c.148G>C	p.Gly50Arg	missense_variant	2/6	ENST00000333279.3	NP_940895.1
LOC105371619	XR_007066737.1	n.943-11963C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD45	ENST00000333279.3	c.148G>C	p.Gly50Arg	missense_variant	2/6	1	NM_198493.3	ENSP00000331268	P1
ANKRD45	ENST00000367712.2	n.179G>C		non_coding_transcript_exon_variant	2/2	1
	ENST00000693292.1	n.323-11963C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 23, 2021

The c.148G>C (p.G50R) alteration is located in exon 2 (coding exon 1) of the ANKRD45 gene. This alteration results from a G to C substitution at nucleotide position 148, causing the glycine (G) at amino acid position 50 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	0.94	N
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-173628410;