4-163512852-C-G

Variant names:

• chr4-163512852-C-G
• rs747108765
• NM_018352.3:c.147C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018352.3(TMA16):​c.147C>G​(p.Asn49Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TMA16 NM_018352.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265
• Publications: 0 publications found

Genes affected

TMA16 (HGNC:25638): (translation machinery associated 16 homolog) Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32150108).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018352.3. 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
	TMA16	NM_018352.3	MANE Select	c.147C>G	p.Asn49Lys	missense	Exon 3 of 7	NP_060822.2	Q96EY4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMA16	ENST00000358572.10	TSL:1 MANE Select	c.147C>G	p.Asn49Lys	missense	Exon 3 of 7	ENSP00000351380.5	Q96EY4
	TMA16	ENST00000509657.5	TSL:5	c.261C>G	p.Asn87Lys	missense	Exon 3 of 7	ENSP00000425347.1	H0Y9X1
	TMA16	ENST00000911660.1		c.147C>G	p.Asn49Lys	missense	Exon 3 of 7	ENSP00000581719.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454500 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 723214

African (AFR) AF: 0.00 AC: 0 AN: 33378

American (AMR) AF: 0.00 AC: 0 AN: 44538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25892

East Asian (EAS) AF: 0.00 AC: 0 AN: 39554

South Asian (SAS) AF: 0.00 AC: 0 AN: 85114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107130

Other (OTH) AF: 0.00 AC: 0 AN: 59998

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.084	T
Eigen	Benign	0.048
Eigen_PC	Benign	0.018
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		-0.27
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.21
Sift	Uncertain	0.023	D
Sift4G	Benign	0.092	T
Polyphen		0.29	B
Vest4		0.22
MutPred		0.51		Loss of catalytic residue at N49 (P = 0.0264)
MVP		0.40
MPC		0.13
ClinPred		0.98	D
GERP RS		1.2
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.46
gMVP		0.33
Mutation Taster		=70/30	polymorphism

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: rs747108765; hg19: chr4-164434004;