1-32075035-A-G

Variant names:

• chr1-32075035-A-G
• rs1051594832
• NM_018056.4:c.89A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018056.4(TMEM39B):​c.89A>G​(p.His30Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 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. H30L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM39B NM_018056.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.62
• Publications: 1 publications found

Genes affected

TMEM39B (HGNC:25510): (transmembrane protein 39B) Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20377666).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018056.4. 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
	TMEM39B	NM_018056.4	MANE Select	c.89A>G	p.His30Arg	missense	Exon 2 of 9	NP_060526.2	Q9GZU3-1
	TMEM39B	NM_001319677.2		c.-293A>G		5_prime_UTR	Exon 2 of 9	NP_001306606.1	Q9NW51
	TMEM39B	NM_001319678.2		c.-273A>G		5_prime_UTR	Exon 2 of 7	NP_001306607.1	Q9GZU3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM39B	ENST00000336294.10	TSL:1 MANE Select	c.89A>G	p.His30Arg	missense	Exon 2 of 9	ENSP00000338165.5	Q9GZU3-1
	TMEM39B	ENST00000441402.5	TSL:1	n.89A>G		non_coding_transcript_exon	Exon 2 of 7	ENSP00000390889.1	F8WB89
	TMEM39B	ENST00000969125.1		c.89A>G	p.His30Arg	missense	Exon 2 of 10	ENSP00000639184.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.051	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.6
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.12
Sift	Benign	0.88	T
Sift4G	Benign	0.60	T
Polyphen		0.98	D
Vest4		0.24
MutPred		0.21		Gain of MoRF binding (P = 0.0099)
MVP		0.31
MPC		1.4
ClinPred		0.91	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.053
gMVP		0.36
Mutation Taster		=67/33	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: rs1051594832; hg19: chr1-32540636;